Sách Giáo Khoa Về Lột Da Hóa Học (Chemical Peels – Ấn Bản 2)

42      Textbook of Chemical Peels
an antioxidant, chelator, and buffer that helps break down cor-
neodesmosomes and makes it easier for the TCA to penetrate
the epidermis. Ascorbic acid has a dual role, acting as a buffer
and protecting against free radicals. It protects the solution as
well as the skin from oxidation.
Prepeel ETCA versus Prepeel TCA–SAS
TCA–SAS should be preceded by several weeks of skin prep-
aration to even out and reduce the thickness of the stratum
corneum, reduce melanocyte activity, and enhance reepitheli-
alization. ETCA, on the other hand, is applied on unprepared
skin, as the acid and the postpeel cream penetrate evenly; the
risk of pigmentary changes (basic protocol) is extremely low
and reepithelialization takes place without prestimulation.
Calculating the Solution Mix
Preparing a TCA–SAS solution appears easy at first sight, but
numerous factors come into play that can change the behavior
of a solution, gel, or paste considerably.
ETCA provides a standardized solution that always pro-
duces the same results when the same protocol is used.
Herpes Prevention
Herpes prevention is essential before a TCA–SAS peel, as the
dermis of the skin has to be destroyed for the peel to be effec-
tive, and the skin’s immune defenses suffer from this destruc-
tion. ETCA is more stimulating than destructive; it will not
destroy the skin’s immune defenses. On the contrary, repeated
peels appear instead to stimulate it. No herpes prevention is
necessary before using ETCA in the “basic protocol” (scattered
pinpoint or cloudy white frosting).
Bacteria Prevention
For the same reasons outlined earlier, the risk of secondary bac-
terial infection is considerably lower with ETCA than with TCA–
SAS. Systematic prevention of infection is not necessary with
ETCA: no antibiotics, no disinfectants. The Langerhans cells
(LCs) in the epidermis and papillary dermis are not destroyed,
nor are the other antigen-presenting cells, and they continue
to prepare the body’s defenses against microscopic predators.
The lymphocytes, macrophages, and other defense cells remain
present in the dermis. The “postpeel cream,” applied as soon
as the first epidermal pinpoint frosting appears, contains treti-
noin precursors that boost the LCs and improve their antigen-
presenting function.
Immediate Prepeel
With a TCA–SAS peel to the papillary or reticular dermis, the
patient’s skin needs to be properly cleansed, cleaned of makeup,
disinfected (with alcohol), and degreased (with acetone). The
doctor must disinfect his hands properly, and the patient must
be kept away from any potentially infectious staff. The TCA–
SAS cannot penetrate the skin properly through grease and
makeup, and the skin must be disinfected to limit the risk of
postpeel secondary infection.
ETCA is usually applied without any prior cleansing,
makeup removal, degreasing, or disinfection. The peel solution
can even be applied on top of makeup, as the emulsifiers in the
base solution hold these molecules in suspension and allow the
TCA to come into contact with the skin. The endpoint of ETCA
treatment is scattered pinpoint frosting or cloudy white frost-
ing, and there is therefore no need to increase penetration of the
peel solution artificially.
Makeup removal, disinfection, and degreasing are not for-
bidden before an ETCA peel, but could increase skin permeabil-
ity and cause the solution to penetrate too deeply and destroy the
dermis. A TCA to the dermis is not the same as an ETCA peel.
Depth of Peel
TCA–SAS is applied with a view to destroying damaged (usu-
ally sun-damaged) skin structures and benefiting from the skin
regeneration that naturally follows a peel. It is really effective
when it destroys the papillary dermis.
With ETCA, the aim is not to destroy the dermis in the
hope of its rebuilding later, but rather to stimulate all the phe-
nomena of skin repair repeatedly, in all the different layers
of the skin. With frequently repeated ETCA sessions (every 8
days), the sum of the results is comparable to that of a papillary
peel without any of the drawbacks.
The “basic protocol” for ETCA is intended to reach the
basal layer of the epidermis or the Grenz zone. There are (many)
other deeper protocols, but they are not as straightforward as
ETCA and the risk of complications is relatively much higher.
ETCA is not necessarily a light peel; it can be used to reach all
depths, from the basal layer of the epidermis to the reticular der-
mis, depending on the protocol used. The relatively superficial
action of the ETCA solution (basic protocol) strongly stimulates
the skin regeneration process and increases the permeability of
the epidermis. The ETCA postpeel cream penetrates the skin
more easily, as it is permeabilized by the peel solution.
Anesthesia, Pain, and Monitoring
A TCA–SAS peel to the dermis is painful and requires the use
of analgesics. Some resistant patients can tolerate a peel reach-
ing the superficial dermis but are left with such unpleasant
memories that they might well refuse further treatment. A
peel to the papillary dermis should not be done without facial
nerve blocks (FNB) and/or sedation. Performing FNB requires
Normal membrane structure:
active transmembrane protein
Lipid breakdown:
inactive transmembrane protein
Figure 5.16  Effect of surfactants on cell membranes.

Selection of the right peel      43
a series of measures, including pulse oximetry at the very least.
Any painful intervention can trigger vagal reactions for which
the doctor must be prepared. Pain after a peel can be dealt with
easily by prescribing oral analgesics (e.g., acetaminophen or
codeine/acetaminophen).
ETCA does not require any type of anesthetic, sedation,
or analgesics. Any mild pain caused by the application of the
ETCA solution can be dealt with immediately, as soon as frost-
ing occurs, by applying the postpeel cream.23 No pulse oxim-
etry monitoring is necessary and no vagal reaction has been
described, perhaps because it is a short procedure.
Length of Peel
It takes 10 minutes to apply ETCA to the basal layer or the Grenz
zone, from the time patients lie down to when they get up.
Applying a TCA–SAS peel, usually to the papillary der-
mis, takes a lot longer: at least an hour should be allowed for
settling the patient in, disinfection, makeup removal, setting
up the monitoring equipment, FNB or sedation, a series of
applications, and letting the patient rest after the peel.
Postpeel Care Day 1 to Day 8
Post-ETCA care consists simply of asking patients to protect
their skin from the sun (Melablock®-HSP) and to apply the most
suitable cosmeceutical for their particular problem (see Chapter
3). They should start the first day after the first of the four peels
and continue until the end of the sixth week after the last peel.
The posttreatment care after a TCA–SAS peel is more complex
and needs much closer monitoring, as the risk of complications
is much higher. Follow-up monitoring after a TCA peel to the
papillary dermis is described in Chapter 23.
Repeating Peels
A TCA–SAS peel can only be repeated after a rest period of
usually 6 weeks to allow the skin to regenerate completely. It
provides a single strong stimulation that decreases with time.
ETCA is repeated four times at weekly intervals to pro-
vide ideal stimulation of the skin regeneration processes. The
postpeel cream and ETCA application technique allows for this
repetition.
If the ETCA were repeated less often (once every 2–3
weeks), the effects of stimulation would not be cumulative.
Weekly repetition, in contrast, “stimulates the stimulation”
resulting from the previous peel.
Combination Treatments
TCA–SAS allows few concomitant combinations, and most of
the treatments that one might wish to combine it with must be
carried out 8–15 days before the peel. For example, nothing can
be injected immediately before a TCA–SAS peel. It is, of course,
possible to inject botulinum toxin in the upper part of the face
just before or after applying a TCA–SAS peel to the area around
the lips, but the toxin should not be injected before applying a
TCA–SAS peel in the same area. The immediate inflammation
induced by the peel could cause the toxin to migrate.
ETCA, on the other hand, allows all concomitant
combinations.
Botulinum Toxin
This can be injected immediately before applying ETCA in the
same area. The technique is simple: inject the toxin, wait 5 min-
utes, apply the ETCA until pinpoint frosting appears, and then
apply the postpeel cream. The cream has an immediate and
pronounced anti-inflammatory effect, which prevents edema
and toxin migration.
The restructuring of the skin by the peel improves the
results of the toxin, and resting the muscles improves an even
collagen deposition.
Filling Wrinkles
Filling techniques can also be used immediately before ETCA,
as the ETCA postpeel cream soon stops inflammation and oxi-
dation. The cream can also absorb the free radicals that are
released by the peel and that could damage the three-dimen-
sional structure of dermal fillers, such as hyaluronic acid. In
fact, the instructions for most dermal filler products specify not
to apply a peel after the filler, but this does not apply to ETCA.
Flashlamps
ETCA can be used after flashlamp treatment24 when treating
pigmentation or photoaging on the face, décolletage, or hands.
It is preferable to start with the lamp and to follow up with the
peel, for the following reasons:
•
Epidermal permeability does not seem to change signifi-
cantly after the lamp, and there is no marked change in
the penetration of the ETCA. Caution is, however, advised
when applying ETCA solution to make sure that it does
not penetrate the skin further than anticipated: the cot-
ton-tipped applicators should be squeezed out properly
after the first application and the treatment should not go
beyond scattered pinpoint frosting.
•
Applying ETCA and the postpeel cream before the flash-
lamp would change the refractive and diffractive proper-
ties of the epidermis, as well as its water content and color.
Risk of Complications
ETCA carries far fewer risks for the patient than TCA–SAS.
Infections
As described earlier, no herpes or bacteria prevention is neces-
sary with ETCA, unlike TCA–SAS.
Risk of Exhausting the Skin’s Resources
At the level of the dermis, the fibroblast is a cell of major inter-
est in understanding how peels work. Like Langerhans cells,
fibroblasts have dendritic morphology; they are fusiform or
stellate but have no antigen-presenting activity. Fibroblasts
synthesize all the constituents of the extracellular matrix and
play an essential role in the formation and contraction of granu-
lation tissue during wound repair. Peels to the dermis destroy a
large number of fibroblasts, and the survivors must multiply in
order to reconstitute the fibroblast population. Each time they
do this, their telomeres shorten, which gradually exhausts their
capacity for future multiplication. Peels to the dermis should
therefore not be repeated too often. ETCA, on the other hand,
does not destroy dermal fibroblasts (and there is no shortening
of telomeres) but stimulates their metabolism and obliges them
to produce more and more rapidly. Logically, repeating ETCA
(basic protocol) cannot accelerate skin aging, which is not the
case with repeated peels to the dermis.
Scarring
During the healing process, hybrid cells, known as myofibro-
blasts, appear in the dermis. They have the morphological

44      Textbook of Chemical Peels
characteristics of both fibroblasts and smooth muscle cells.
They are responsible for tissue contraction–retraction during
healing. Their cytoplasm contains networks of myofilaments
that are in contact with specialized zones of the plasma mem-
brane and can interact with the adjacent cells or connective
tissue. These myofibroblasts appear to be differentiated fibro-
blasts that have acquired the properties of smooth muscle cells.
Controlled stimulation with DMAE, for example, is a good way
to achieve a tightening effect on the skin.
Correlating this theoretical data with the clinical data on
peels is not without interest, as it allows us to anticipate which
peels might potentially cause scarring and which ones will
not. Deep peels, which go beyond the upper reticular dermis
and practically lay the hypodermis “bare,” are more danger-
ous as far as retractile scarring is concerned, as they stimulate
the conversion of fibroblasts into retractile myofibroblasts that
can cause scarring. Not all agents are equally potent; there are
more descriptions in the literature of problems with scarring
with deep TCA peels than with phenol-based peels. There is no
reason why peels that do not go beyond the Grenz zone should
stimulate the conversion of fibroblasts into myofibroblasts, as
there is no “laying bare” of the internal tissue and hence no need
for retraction. Retractile scar reactions are therefore extremely
rare with the basic ETCA protocol; they can only occur when
the peel has not been applied correctly. Peels that reach the
Grenz zone or the papillary dermis stimulate small fibroblasts
that are parallel to the epidermis and have dendritic processes
that connect with several collagen and elastin bundles. The
synthesized collagen is aligned horizontally in the border zone
(Grenz zone), and the resulting tension from the activity of any
potential myofibroblasts produces a positive cosmetic effect:
improved tension in the papillary dermis, which can be called
the “lifting effect.” The “lifting effect” achieved with medium-
depth peels in no way compares with the lift achieved when
sagging skin and muscle mass are treated surgically. In some
cases, doctor and patient can be sent off on the wrong track and
delay taking the often dreaded and sometimes formidable deci-
sion to go ahead with surgery.
Postinflammatory Hyperpigmentation (PIH)
It is clear from the medical literature on chemical peels that
TCA–SAS is the agent responsible for the majority of post-
peel pigmentary problems. Photographs abound in specialist
books. A TCA–SAS peel does in fact cause severe inflamma-
tion after the peel, and it is therefore not surprising to come
across many cases of PIH.25 ETCA in the basic protocol causes
almost no PIH.
Generally, IV, V, and “light VI” skin phototypes are at
greater risk of PIH.
Downtime
During the postpeel period after a TCA peel to the papillary
dermis, the patient has to put up with a week of edema, scab-
bing, erythema, pain, and other inconveniences. Any form of
social life is out of the question, and the patient can only return
to normal social activities, with the help of makeup, after the
eighth day. It is several weeks before the skin returns to normal.
With ETCA (basic protocol), on the other hand, the patient can
lead an almost perfectly normal social life, as the flaking is no
more serious than with sunburn and only lasts for 48–72 hours.
NOTES
1. Although some peels with an alkaline formulation do exist.
2. Apart from Easy Phytic Solution, whose acids can penetrate to
the papillary dermis.
3. With Easy TCA and Easy Phytic, papulopustular acne can be
treated during its active phase.
4. Dimethylaminoethanol, a precursor of acetylcholine. See the
section on DMAE in Chapter 3.
5. Blending Bleaching Cream (see ).
6. By injecting phophatidylcholine/deoxycholate into under-eye
bags, there is a risk—among other complications—of disrupting
the adipocyte cell walls as well as the muscle cells that come into
contact with this product. Moreover, it triggers severe and pain-
ful edematous erythema that lasts several days and is only effec-
tive after several sessions. For the moment, fatty bags under the
eyes can only be treated surgically.
7. Source: Dr. Robert Vergereau, Spain.
8. For example, Renutriv ACE Lipoic Complex: vitamins A + C + E
and lipoic acid.
9. See the section on the area around the mouth in Chapter 37.
10. The same applies for Easy Phytic Solution.
11. For example, Purifying Cream by Skin Tech.
12. Depending on preliminary examination of the patient and the
doctor’s experience: dermal filling, botulinum toxin, cannula-
tion, threading, etc.
13. Either four Easy TCA peels to the basal layer or a Unideep peel to
the papillary dermis.
14. See Chapter 34 for application of the Lip & Eyelid Formula.
15. Although it must be taken into account that four peels to the Grenz
zone are not necessarily as efficient as one peel to the papillary
dermis. The latter can destroy a large number of lesions that peels
to the Grenz zone do not always reach.
16. Some studies suggest that DMAE can eliminate the lipofuchsin
in lentigines.
17. As the much missed Dr. Yoram Fintsi called it.
18. To avoid leaving an obvious demarcation line.
19. This is a permanent polyalkylimide filler in the form of a remov-
able endoprothesis. Fat transfer is used more often, as there is no
risk of rejection and the implant is autologous.
20. See the details of melasma treatment in Chapter 15.
21. The “burning” sensation soon improves on application of a cold
pack.
22. SLES is not the same as sodium lauryl sulfate (SLS, also known
as sodium dodecyl sulfate [SDS]), a powerful surfactant and very
irritating to the skin, with which it is often confused.
23. It is not neutralizing, however, as we shall see later.
24. Provided that this is classic flashlamp treatment and not a device
combining pulsed light and radiofrequency, for example. These
machines significantly change skin permeability and can cause
the acids to penetrate too far, with the risk of scarring.
25. See Chapter 37 for more details.

6
Alpha hydroxy acids
Chemistry, pH and pKa, and mechanism of action
Alpha hydroxy acids (AHAs) occur naturally in a number of
fruits (hence their “eco-friendly” name of fruit acids) and dairy
products. This class of acids contains a number of molecules
that have in common the presence of a carboxylic acid group
(COOH) and a hydroxy group (OH) in the alpha position rela-
tive to the acid group (Figure 6.1). As early as 1946, the applica-
tion of a 3% lactic acid solution at pH 3.8 was already considered
a treatment for ichthyosis, although cosmetic dermatologists
started using AHAs when in 1974 Van Scott and Yu described
how effective they were in the treatment of dry or ichthyotic
skin. From then on, the scope of AHAs broadened, and some
authors reported their beneficial effects on acne, photoaging,
and benign hyperplastic epidermal lesions. It was often sug-
gested that AHAs should be used to treat age-related wrinkles
and sagging skin. Although the direct target of AHAs seems to
be corneodesmosomes, the indirect action of topically applied
AHAs affects not only the whole of the epidermis but also the
papillary dermis and the pilosebaceous units. However, while
all peels produce similar1 histological effects on the different
layers of the skin, clinical results clearly show that AHAs, used
as light peels, do not improve the skin’s appearance to the same
extent as TCA or phenol. Moreover, indications for glycolic acid
peels tend to be restricted to the treatment of sun-damaged or
acneic skin, especially in patients who cannot or do not want
their skin to flake, often because of their professional activities,
which are incompatible with visible peeling.
A number of AHAs have been proposed for medical use:
glycolic acid, lactic acid, malic acid (with two COOH groups),
tartaric acid (with two OH and two COOH groups), citric acid
(with three COOH groups), and mandelic acid (which has an
aromatic (phenyl) group attached to the alpha carbon atom). See
Table 6.1.
GLYCOLIC ACID
Glycolic acid (hydroxyethanoic acid, hydroxyacetic acid) is
the shortest AHA, with just two carbon atoms (Figure 6.2). It
was originally extracted from sugar cane, but the acid used in
treatment today is synthesized chemically. AHAs have become
popularized as “fruit acids,” and this benign-sounding name
has had a great influence on the interest shown by patients.
The situation is similar to that when patients talk of lasers, gold
threads, or caviar rejuvenating creams. These words evoke
dreams of miracle cures in the imaginations of some: odorless,
colorless, and painless, permanently effective and, of course,
without side-effects.
Glycolic acid is extremely hydrophilic, and a pure aque-
ous solution of glycolic acid, saturated at a concentration of
about 80%, has a pH of 0.5. This pH, considerably lower than its
pKa of 3.83, shows that the solution consists mostly of pure acid
and is effective for performing a peel. The pH of a glycolic acid
solution determines its acidifying power on the skin: a 3% gly-
colic acid solution at pH 3 can acidify the first five layers of cor-
neocytes, whereas at 10% and pH 3, it causes a deeper and more
rapid acidification of the epidermis.2 Note that “acidification of
the epidermis” does not mean “peeling effect.” Acidifying sev-
eral layers of the skin does not necessarily mean destroying the
cells. Up to a certain point, cells resist acidification.
LACTIC ACID
Lactic acid (2-hydroxypropanoic acid, α-hydroxypropionic acid)
is the next shortest AHA after glycolic acid. A methyl group
(CH3) replaces the terminal hydrogen atom on the alpha car-
bon (Figure 6.3). It has a pKa of 3.86, which is close to that of
glycolic acid. Lactic acid occurs naturally in sour milk. After
penetrating the skin, lactic acid is converted automatically and
reversibly into pyruvic acid, the alpha-keto acid derivative of
lactic acid: a keto (= O) function replaces the hydroxy (–OH)
function on the alpha carbon. At identical concentrations, lactic
acid destroys the epidermis more slowly than glycolic acid.
Concentrations of lactic acid of 10%–20% or stronger
begin to destroy the stratum corneum and stimulate skin
regeneration, the renewal of epidermal cells. However, some
studies have shown that cell renewal is not maintained uni-
formly during long-term treatments with 3% lactic acid at pH 3.
In fact, cell renewal gradually falls off during the first 10 weeks
of treatment with 3% glycolic or lactic acid at pH 3, decreasing
to 29.3% and 28.3%, respectively.3 When applied regularly, lactic
and glycolic acids (at 3%, pH 3) lose a significant percentage of
their capacity to destroy corneocytes and renew the epidermis
around the 12th week. Salicylic acid (a beta-hydroxy acid), on
the other hand, retains its ability to destroy corneocytes much
longer.
At a concentration of 50%–70%, lactic acid produces the
same amount of exfoliation as glycolic acid. As early as 1974, it
had been shown that lactic acid improved skin hydration and
suppleness and that a pH of 3 was more effective than a pH
of 5. Lactic acid is also a better hydrator than urea or glycerol.
Some studies tend to show that 3 weeks of daily application of
12% lactic acid would allow as much collagen to be deposited
in the papillary dermis as applying 25% trichloroacetic acid
(TCA) or phenol. We must remember, however, that histologi-
cal findings, as important as they are, do not always translate
into cosmetically visible clinical results and that laying down
new collagen is only one of the changes associated with peels.
OTHER HYDROXY AND KETO ACIDS
Many other hydroxy acids (and the related keto acids) are used
in cosmetic treatments (Table 6.1).
Ascorbic acid (vitamin C) is an AHA derivative. It has
been shown to stimulate collagen production and reduce

46      Textbook of Chemical Peels
melanin production. Under identical conditions, classifica-
tion of the acids described thus far in this chapter in order of
strength would give the top three as:
1.
Glycolic acid
2.
Lactic acid
3.
Mandelic acid
In the rest of this chapter, it is mainly the use of glycolic
acid that will be discussed, and by default this is what the
information given applies to.
It is clear, however, that as a general rule, and even if
some acids have specific properties, most of the hydroxy acids
(alpha or beta), carboxylic acids (containing the COOH group),
dicarboxylic acids, and alpha-keto acids produce the same posi-
tive effects on the skin, depending on the concentration, the pH
of the solution (Figure 6.4), and how they are applied.
BUFFERS
In low concentrations, the pH of a glycolic acid solution var-
ies with the concentration of acid: an unbuffered glycolic acid
solution, at less than 1%, has a pH of approximately 2.5.4 At 2%,
the pH is 2.1. When the concentration reaches 5%, the pH goes
down to 1.9. It is 1.7 for a 10% unbuffered glycolic acid solu-
tion. Higher concentrations, 50%–80%, have a pH close to 0.5.
At identical pH about 0.5, a solution with a concentration of 80%
is more aggressive than a 50% solution (Boxes 6.1 to 6.4).
A concentrated glycolic acid solution at pH 0.5 consists of
free and active acid, and is aggressive to the skin. It is a thousand
BOX 6.1  Importance of Buffers in the Body
The body’s—and the skin’s—enzyme reactions are pH-sen-
sitive. It is vital for the body to keep the pH of an organ stable
in order to stabilize enzyme reactions. Protection against pH
variations—the buffer capacity—must be extremely active
and strong, as natural metabolic processes permanently
synthesize acids and alkalis that are liable to modify the pH.
The blood, for example, is protected by two important
buffer systems: the hemoglobin system and the bicarbonate
system, which stabilize its pH between 7.37 and 7.43. The
bicarbonate system is the most important buffer for plasma
and interstitial fluids. Neutralizing the skin with sodium bicar-
bonate is the most “natural” method.
BOX 6.2  Effect of Dilution on the pH of a Solution
Five ml of the base solution has pH 2.7–3. Adding 20 cm3
of water does not change the pH. The total volume must
be brought up to 85 ml for the pH to rise from 3 to 4. See
Figure 12.9.
Hydroxy
group
OH
R — Cα — C
H
OH
O
Carboxylic
acid group
Figure 6.1  General chemical structure of an alpha hydroxy acid.
α indicates the alpha carbon atom; R represents a general organic
group.
Table 6.1  Hydroxy and Keto Acids Used in Cosmetic Treatments
Acida
pKa
Chemical structure and alternative names
Tartaric acid
pKa1 = 3.02
HOOC.CH(OH).CH(OH).COOH
pKa2 = 4.54
(+)-2,3-dihydroxybutanedioic acid;
d-2,3-dihydroxysuccinic acid (only the dextrorotatory [+, or d] form is active)
[dicarboxy dialpha-hydroxy acid]
Citric acid
pKa1 = 3.06
HOOC.CH2.C(OH)(COOH).CH2COOH 2-Hydroxy-1,2,3-propanetricarboxylic
MW 192.13
pKa2 = 4.74
acid
pKa3 = 5.40
[Tricarboxy alpha-hydroxy acid]
Mandelic acid
pKa = 3.36
C6H5.CH(OH).COOH
MW = 122.14
(+)-phenylhydroxyethanoic acid; d-α-hydroxyphenylacetic acid; d-phenylglycolic acid;
amygdalic acid [alpha-hydroxy acid]
Pyruvic acid
pKa = 2.50
CH3.CO.COOH
MW = 88.06
2-Oxopropanoic acid; acetylformic acid; α-ketopropionic acid; pyroracemic acid
[alpha-keto acid]
Malic acid
pKa1 = 3.40
HOOC.CH2.CH(OH).COOH
MW = 134.09
pKa2 = 5.5
hydroxybutanedioic acid; hydroxysuccinic acid, [dicarboxy alpha-hydroxy acid]
HOCH2.(CHOH)4.COOH
2,3,4,5,6-pentahydroxyhexacetic acid
d-Gluconic acid
pKa = 3.86
α,β,γ,δ,ε-pentahydroxycaproic acid; dextronic acid; glycogenic acid; glyconic
MW = 196.16
acid; maltonic acid [alpha-hydroxy acid]
Salicylic acid
pKa = 2.98
HO.C6H4.COOH
MW = 138.12
o-Hydroxybenzoic acid, [beta-hydroxy acid]

ALPHA HYDROXY ACIDS: CHEMISTRY, pH AND pKa, AND MECHANISM OF ACTION      47
times more acidic than a solution at pH 3.5.5 A solution this
strong needs to be properly neutralized by the doctor applying
it. Applying a 70% non-neutralized glycolic acid solution to the
skin can destroy the epidermis in 2–7 minutes, depending on
the skin type, the thickness of the stratum corneum, the degree
of photoaging, and the prepeel preparation of the skin.
Applying large quantities of pure acid to the skin (during
a glycolic acid peel with a non-neutralized solution) saturates
its natural buffer capacity, and the excess acid must be neutral-
ized to avoid burning the skin.
The contact time for a glycolic acid peel, as well as for
other AHAs, is the time between applying the peel6 and neu-
tralizing it. The contact times for partially buffered AHAs, at
pH > 2.5, are far longer than for pure unbuffered AHA solu-
tions at pH 0.5,7 which are a hundred times more acidic.
pH of Human Skin
The pH values on the surface of normal skin vary between
4.5 and 6, and up to a certain point the skin has the ability to
defend itself against pH variations and can maintain a stable
pH in the face of moderate acid or alkali attacks.
When going deeper into the dermis, liquid and nutrients
coming out of blood vessels are more and more concentrated
and the dermis has the blood pH: 7.2. Liquids and nutrients are
frequently replaced; this gives a permanent renewal of the skin
buffer capacity.
Neutralizing an AHA peel consists in applying a base solu-
tion (usually pH 9–10) to the treated area. Rinsing with water
only dilutes the acid without neutralizing it (Box 6.2); an acid is
neutralized by a base. However, dilution does have the merit of
reducing the proton concentration8 and so eventually increases
the pH (without changing the pKa, of course) when enough
water is added. The high acidity of concentrated and unbuffered
AHA solutions, as well as the complications that stem from such
treatments, has brought the pH of many glycolic acid solutions
to around pH 4–5.5.9 Ammonium salts, sodium bicarbonate, or
sodium hydroxide (NaOH) are often used for this. The resulting
BOX 6.3  pH
pH is a measure of the acidity or basicity of a water solution.
pH = The “p”ower of H+ = pH = proton concentration
Solutions with a pH less than 7 are said to be acidic;
solutions with a pH greater than 7 are basic or alkaline.
Pure water has a pH very close to 7, while tap water is pH
+/- 5.5–6. Nonwater solutions have no pH: pH of oleic acid
cannot be measured.
BOX 6.4  pOH
pOH is a measure of the alkalinity of an aqueous solution.
Solutions with a pH greater than 7 are said to be basic or alka-
line. pOH ≅ 14 – pH. This measure of alkalinity is rarely used,
since the same result can be more easily expressed in pH.
Acidic
Basic
0
1.5
3
5.5
7
9.5
11
12.5
14
Easy TCA®
Unideep®
Lemon
juice
Red
wine
Milk
Saliva Egg white
Seawater
70%
unbuffered
glycolic acid
Gastric
juices
Coca Cola®
Vinegar
Beer
Phenol
peel
Human blood
Tears
EMLA
Sodium
bicarbonate
Ammonia
1 M NaOH
1 M HCl
pH 3 is 10 times more acidic than pH 4
pH 3 is 100 times more acidic than pH 5
pH 0.5 is 1000 times more acidic than pH 3.5
Figure 6.4  pH of various substances.
H3C
C
C
OH
O
H
HO
Figure 6.3  Chemical structure of lactic acid.
H
C
C
OH
O
H
H
Figure 6.2  Chemical structure of glycolic acid.

48      Textbook of Chemical Peels
chemical reaction produces a salt10 and water—the pH increases
and the potency of the acid solution decreases:
glycolic acid + NaOH ← sodium glycolate + H2O
Hydronium
Hydronium is a synonym of oxonium (trivalent oxygen cation)
(Figure  6.5). Hydronium is the cation that forms from water
in the presence of hydrogen ions (H+ coming from acids).
Hydronium does not exist in a free state: it is extremely reac-
tive and solvated by water, liberating H+. The supplementary
H+, stuck on a normal H2O molecule and giving it the form of
hydronium, can still build electrical links with another H2O of
the neighborhood, forming a “Zundel cation” in which one H+
finally interacts, very transitorily, with 2 water molecules.
When an acid liberates a proton in solution, this proton
links with one or more water molecules to form hydronium
molecules. Hydronium itself is very active and unstable, and
immediately exchanges protons with neighboring water mol-
ecules or living structures. The activity of oxonium/hydro-
nium cations is not relevant when speaking about peelings
because, finally, it is created by the free proton, moving from a
water molecule to another one. In fact, when hydronium is in
phase of “existence,” the H+ is not able to interact with living
structures.
Hydronium is not a way of stabilizing an acid, because
the structure itself is so quickly transient that it can be consid-
ered as not existing.
pKa
The natural pH of an aqueous solution of 60% glycolic acid is
0.5. The gradual addition of a base slowly raises the pH of this
solution. When the pH reaches a value of 3.83 as a result of the
gradual addition of the base, we know that this solution con-
tains exactly 50% of active free acid and 50% of salt produced
by the reaction of the glycolic acid with the base (e.g., sodium
glycolate or ammonium glycolate).
A pH of 3.83 corresponds to the pKa value of a glycolic
acid solution. If we keep on adding a base solution to the gly-
colic acid solution, the pH will gradually increase, while the
proportion of free and active acid and the strength of the solu-
tion decrease. A glycolic acid solution whose pH had been
brought up to 7 would be completely neutralized or buffered and
inactive. A glycolic acid solution at pH 5 is partially neutralized
or buffered and partially inactive, as it does not contain much free
acid. It is far less aggressive to the skin, of course, but it is also
less active.
The pKa is therefore an important notion that allows us
to understand and anticipate how aggressive an AHA peel
solution will be, on condition that we also know the pH of the
solution. Knowing the pKa alone, which is a definitive and set
parameter for each acid, does not help determine how aggres-
sive a peel solution is. The pKa of glycolic acid is and will always
be 3.83, whereas the pH of the solution could vary between
0.5 and 7 or above. The greater the pH than the pKa of an acid
solution is, the less aggressive it will be. The lower the pH than
the pKa of an acid solution is, the more aggressive it will be. It is
therefore not possible to choose the pKa of the solution that we
want to use, as this parameter has been determined chemically,
once and for all, for each acid, and it gives the exact pH at which
50% of the active molecules remain. We can, on the other hand,
change the pH of the solution and make it lower than the pKa
to make the solution more aggressive. We can also raise the pH
above the pKa to soften the effect.
A partially neutralized solution at pH  4 still contains
enough free acid to achieve a clinical effect but is far less effec-
tive than a solution at a lower pH. Partial neutralization of a
glycolic acid solution is therefore a compromise between effect
and risk. It is, in fact, surprising that glycolic acid is still par-
tially active at pH levels of around 5. It seems that the alpha
position of the hydroxy group in a small molecule like glycolic
acid is the reason for this partially maintained effectiveness,
even if the pH is relatively high. Other AHAs do not appear to
remain active at high pH levels.
Using a partially neutralized solution at pH 4.5 achieves
the same results in a few months that could be obtained in a
few weeks with the same unbuffered concentration. It is there-
fore true to say that it is possible to achieve the same results
using neutralized or non-neutralized peel solutions. But
patients would then have to be convinced to have many more
peels, which, on top of the inconvenience of repeated visits to
the surgery, means more expense—and that is never appreci-
ated. The doctor may think it necessary to sacrifice effective-
ness for safety, but the patient usually thinks that the doctor
should find a quicker and more effective solution without sac-
rificing safety.
An application of dansyl chloride accumulates in the epi-
dermis and stains the skin. It is possible to measure the rate of
disappearance of this coloration after the application of differ-
ent hydroxy acid solutions at a constant pH. The rate at which
the color disappears is correlated with the rate of cell replace-
ment, and therefore provides information on the stimulation of
epidermal turnover and on the capacity of the acid to stimulate
skin regeneration.
Partial neutralization of these solutions, to pH  5, quite
clearly reduces the rate of renewal, and neutralizing these same
solutions to pH  7 removes all of their clinical effectiveness
(Table 6.2).
The ultimate goal of treatment with AHAs is to stimulate
skin regeneration at the same time as avoiding as far as pos-
sible the side effects that stem from their irritant potential. It is
not easy to achieve this goal, as a very acid pH is required to
ensure optimum clinical effectiveness. The aggressiveness of
these acid solutions usually entails a higher risk of complica-
tions. It is possible, however, to use a solution made up of differ-
ent AHAs at a concentration higher than 60% and pH 0.5, at the
same time as limiting the risk of complications: Easy Phytic is
Table 6.2
Type of acid
Concentration, pH
Skin renewal
stimulation, up to:
TCA
0.5%, native pH
50%
Lactic acid
4%, pH 3
34%
Acetic acid
3%, pH 3
30%
Pyruvic acid
4%, pH 3
23%
O
H
H
+
H
Figure 6.5  Hydronium.

ALPHA HYDROXY ACIDS: CHEMISTRY, pH AND pKa, AND MECHANISM OF ACTION      49
an unbuffered solution of three AHAs, at pH 0.5. This solution
uses a slow-release technology that does not need neutralizing
in spite of its very acid pH, which is much lower than its pKa.
MECHANISM OF ACTION
AHAs do not coagulate proteins. Applying them in a peel
therefore should not produce a “whitening effect.” According
to Forestier, the mechanism of action of AHAs is as follows.
Even at low concentrations, AHAs can insert themselves
between two protein chains. Here, they build a sort of bridge
that reduces corneocyte cohesion. As a result of the lytic action
of AHAs on corneodesmosomes, corneocytes are shed more
easily from the skin, and the thickness of the stratum corneum
is reduced. The skin appears more hydrated as the stratum cor-
neum is thinned or disappears temporarily.
AHAs, even at low concentrations, acidify the upper
layers of the skin. Experimentally, at pH < 5, this acidification
causes an increase in the epidermal activity of lipases, phos-
phatases, and transforming growth factor beta (TGF-β). At
higher concentrations, the protein chains are separated from
each other, and this causes epidermolysis—more or less vis-
ible exfoliation. Because of this corneocyte-shedding activity,
AHAs have been used primarily to treat certain hyperkeratini-
zation disorders. Not all corneocytes react in the same way to
AHAs: the more superficial, less hydrated corneocytes seem to
be less sensitive to the action of AHAs than the corneocytes at
the base of the stratum corneum.
AHAs may also limit or prevent the cross-linking of pro-
teins in the extracellular matrix. Unlike TCA or phenol, AHAs
do not bind with proteins and so are not neutralized by them.
The type of action they produce depends on their concentra-
tion, the pH of the solution, the pKa of the acids, and the contact
time with the skin before neutralization with a base solution.
For example, a 70% glycolic acid solution (pH 0.5 for pKa 3.83) in
contact with the skin for 5 minutes will be more aggressive than
a partially buffered (pH 3.5) 50% solution left in contact with
the skin for 2 minutes before neutralization with a base solution
(a saturated solution of sodium bicarbonate, for example).
The type of AHA molecule used is also of prime impor-
tance. Glycolic acid is the most aggressive AHA because it is
the smallest. The type of vehicle used, the skin type, and the
disorder being treated are also factors to be taken into account
when anticipating the action of a peel.
The accelerated shedding of corneocytes disrupts the
protective barrier function of the epidermis. From there, a cas-
cade of secondary events stimulates growth in the basal layer
of the epidermis and accelerates the conversion of keratinocytes
into corneocytes11 to restore optimum barrier function as soon
as possible. Stimulation of the mother cells by the keratinocytes
of the basal layer can unfortunately go hand in hand with reac-
tional and inflammatory melanocyte stimulation, the cause
of potential pigmentary changes.12 The stimulation of kerati-
nocyte growth is also accompanied by positive stimulation of
fibroblast proliferation and synthesis of proteins in the dermis
(collagen, elastin, and glycosaminoglycans).13
Another indirect effect of AHAs, which also comes
from the disruption of the barrier function of the epidermis,
is that they enhance the penetration of other topical agents
with which they are mixed. AHAs are often used as agents to
enhance the penetration of other molecules, in the treatment of
acne or melasma, for example. Histological studies show that
the injury to the skin and the principles of repair are similar
during a peel and during dermabrasion. The extent of repair
is directly related to the depth of injury. In the case of glycolic
acid peels, scabbing occurs only when the peel has penetrated
too deeply. The scab consists of keratin, necrotic keratinocytes,
and a protein precipitate. Glycolic acid may be an antioxidant
and protect against UV radiation through the same mechanism
of action as ascorbic acid, but, given that it reduces the thick-
ness of the stratum corneum, it can also enhance penetration
of UV radiation through the epidermis. Even if the thinning of
the stratum corneum is only temporary, AHAs are therefore
not used to protect the skin against the sun, but can be applied
after exposure for their anti-free-radical effects.
NOTES

1. In quality but not quantity.

2. Pons Gimier L, Parra Juez JL. Ciencia Cosmetica. Consejo General
de Colegios Oficiales de Farmaceuticos, 1995: 285–6.

3. Pons Gimier L, Parra Juez JL. Ciencia Cosmetica. Consejo General
de Colegios Oficiales de Farmaceuticos, 1995: 284–5.

4. A pH similar to that of vinegar or lemon juice.

5. The pH scale is logarithmic rather than linear.

6. Which must be done as quickly as possible so that all areas of the
face are at practically the same level of acid attack at the time of
neutralizing.

7. Except for Easy Phytic, which is not neutralized.

8. An acid is, by definition, a molecule that can donate a proton.

9. Lidocaine with epinephrine (adrenaline) has a similar acid pH,
but it is impossible to do a peel with lidocaine. Acidity is there-
fore not the only important parameter.
10. A salt is formed by the interaction of an acid and a base; an ester
(R–COO–R’ if R’ is not –H) is formed by the interaction of an acid
and an alcohol.
11. Via tumor necrosis factor alpha (TNF-α), among other mediators.
12. Known as postinflammatory hyperpigmentation (PIH).
13. Ammonium lactate has been shown to prevent dermal atrophy
resulting from the use of topical corticosteroids.

7
Alpha hydroxy acids
Histology and factors influencing penetration
HISTOLOGICAL CHANGES
Epidermis
Epidermal regeneration is histologically visible after 2–7 days,
and the epidermis is completely replaced 2 weeks after a sin-
gle light alpha hydroxy acid (AHA) peel. A single application
of a glycolic acid peel (20%–30%) reduces corneocyte cohesion,
which accelerates the elimination of cells in the stratum corneum
and hence reduces the thickness of the epidermis for around 2
weeks (the time it normally takes for the superficial layers of
the epidermis to heal). Using 50% concentrations of glycolic acid
“unglues” the cells in the stratum granulosum. Higher concen-
trations (70%) or a more aggressive mode of application causes
epidermolysis, or skin necrosis, beneath the stratum corneum.
Unlike single applications, daily use of AHAs seems to
thicken the epidermis over time because of the constant stimu-
lation it provides.1 However, other authors suggest instead a
possible thinning of the epidermis in the long term.
Dermis
The histological effects of AHAs also reach the dermis. Moy
showed that fibroblast cultures in a glycolic environment pro-
duced up to 10 times as much hydroxyproline (a precursor of col-
lagen) than when cultivated in a normal saline environment.1 A
practical problem is that AHAs do not normally reach the dermis
(because, apart from Easy Phytic Solution, they are neutralized
before they can penetrate that far) and therefore cannot directly
stimulate fibroblasts as well as they did in this in vitro study.
In the papillary dermis and sometimes even in the
upper reticular dermis, mild edema, an inflammatory reac-
tion, and production of new collagen and elastin are observed.
Production of these dermal components does not appear to be
directly proportional to the extent of the inflammatory reaction.
Glycolic acid stimulates fibroblasts to produce collagen, but not
in the same way as trichloroacetic acid (TCA) or phenol, which
produce a thick horizontal layer of papillary dermal collagen
proportional to the dermal injury and hence the repair caused
by the acid.2 However, the laying down of a new layer of col-
lagen in the dermis is one of the essential elements of cosmetic
improvement and skin rejuvenation. Some studies have pre-
sented biopsies showing the presence of new collagen arranged
horizontally, with a predominance of fibroblasts 2–3 weeks
after a peel.3 This new collagen remains for around 1 year.2 The
concentration of glycosaminoglycans increases and gradually
stabilizes. This effect could be one of the mechanisms respon-
sible for the positive effect of glycolic acid on fine wrinkles (a
filling effect after several peeling sessions).
“Chronic” use of AHAs seems to allow the dermis and
epidermis to thicken gradually and regenerate after an initial
period of flaking that, in contrast, thins the epidermis and
requires the daily use of effective sun protection.
FACTORS INFLUENCING AHA PENETRATION
Other factors also influence the aggressiveness of a glycolic acid
solution (Table 7.1).
Table 7.1  Factors in the Aggressiveness of Glycolic Acid Solution
Factor
Fact
Example
pH
The lower the pH is in relation to the pKa, the more
aggressive the solution is.
Glycolic acid has a pKa of 3.83. A peeling solution of a
given concentration will be more aggressive at pH 1 than
at pH 2.5.
At pH 3.5, by definition, 50% exactly of the glycolic acid
molecules are neutralized, transformed in a salt that is
inactive.
Concentration
The closer the glycolic acid concentration is to 80%
(a saturated solution), the more aggressive the
solution is.
At constant pH, pH:2 for example, an 80% glycolic acid
solution will be more aggressive than a 25% one.
Other
components
of the
solution
Some components can slow down or accelerate the
penetration of AHAs.
Bear in mind the esterification reaction: an organic
acid (R.COOH) reacts with an alcohol (R’.OH) to form
an ester (R.COO.R’) and water: acid + alcohol a
ester + water
R–COOH + R’–OH a R–COO–R’ + H2O
This reaction is slow and reversible.
The ester does not produce a peel.
An alcoholic solution of AHAs would partially consist of
ineffective esters that could be converted back into acid
by shifting the balance of the reaction, after the acids in
the solution have been medically or naturally neutralized.
Applying alcohol to the skin, as a prepeel disinfectant,
does not interfere with the peel if the alcohol is given time
to evaporate.

Alpha hydroxy acids: HISTOLOGY AND FACTORS INFLUENCING PENETRATION      51
NOTES

1. Rubin MG. Manual of Chemical Peels: Superficial and Medium Depth.
Philadelphia: Lippincott, 1995.

2. Moy LS, Mene R. Glycolic Acid Chemical Peel. In: Roenigk R,
Roenigk H (Eds.). Roenigk & Roenigk’s Dermatoligic Surgery,
Principles and Practice. 2nd ed. New York: Dekker, 1996:1103–12.

3. For this reason, it pays to inject botulinum toxin before starting
the peel. Immobilizing the muscle mass will allow the smooth
synthesis of new collagen.

4. Epidermal permeability in descending order: genital organs >
facial skin > skin on torso > skin on upper and lower limbs.
Table 7.1 (Continued)  Factors in the Aggressiveness of Glycolic Acid Solution
Factor
Fact
Example
Preparing the
skin in the
weeks before
the peel
Any treatment that thins the stratum corneum increases
the permeability of the epidermis4 and the speed of
penetration of AHA.
Tretinoin, AHA creams, and benzoyl peroxide are examples
of products that allow AHAs to penetrate more deeply.
Preparing the
skin just
before the
peel
Before an AHA peel, the skin must be cleansed and
degreased, but not aggressively. AHAs are actually
hydrophilic, and fats in the skin reduce their clinical
effectiveness. Degreasing the skin vigorously, by using
an ether swab firmly pressed on the skin for example,
would make it difficult to predict how far the AHAs would
penetrate. Immediately before an AHA peel, the skin
should be cleansed and degreased with alcohol and
acetone (although not aggressively), in contrast to what
can be done before a TCA peel to the papillary dermis
Special attention should be paid to home waxing or
scrubbing before the peel.
Contact time
Neutralizing the peel too soon stops its effect.
Neutralizing too late can potentially cause serious side
effects.
Easy Phytic solution, being self-neutralizing, suppresses
every neutralization problem.
Easy Droxy complex peel is neutralized with a neutralizer
that changes color when pH shifts from acidic to basic.
Neutralization
versus
simple
rinsing
Rinsing with water only dilutes the acid without
neutralizing it. Only the application of a base solution
can neutralize the acid.
Frequency of
repeated
peel
sessions
Repeating peels too often gradually deepens their action
and can cause chemical burns.
Repeating peels after too long a delay does not allow
gradual stimulation of the dermis—the peel will not be
able to achieve its full effects.
A less aggressive peel can be repeated more often than a
more aggressive one: a 25% glycolic acid peel could be
repeated 1 or 2 times/week, while a phenol peel can’t be
repeated before several months (6 weeks in the case of
Lip & Eyelid Formula or Easy Phen light).
Force of
application
of a peel and
type of
applicator
Up to a logical limit, the more forceful the application, the
deeper the penetration.
At constant acid quantity applied on the skin, a brush simply
spreads the acid solution on the stratum corneum,
whereas using gauze causes some abrasion at the
moment of applying the acid solution and makes it
penetrate more deeply.
Cotton buds appear to be a safe and reproducible way to
apply peelings, since the pressure can’t vary too much:
a too strong pressure binds the cotton buds.
Note that a brush could apply more product to the skin
compared to cotton buds, which would induce a more
aggressive peeling.
Skin hydration
and health
Young, healthy, and hydrated skin is less permeable than
skin treated with tretinoin or skin with seborrheic
dermatitis, severe photoaging, or acne.
Aging induces a thickening of the stratum corneum, skin
dryness, and impermeability.
Active acne lesions allow a faster acid penetration, by
stratum corneum disruption.
Volume of acid
applied on
the skin
At the same pH and concentration, applying a greater
volume of acid on the skin induces greater necrosis.
Applying just a few drops of 70% unbuffered glycolic acid
solution on the face will be far less aggressive than
applying 5 ml of the same solution.
Adding coat after coat of a peeling solution progressively
deepens its action.
Other factors
The penetration of AHAs through the skin is also
increased by prior use of certain products.
Such products include:
• Hair-removal products (watch out for the upper lip area)
• Exfoliants (some creams contain fruit acids)
• Preparatory masks and vinyl masks
• Retinoids
• Hair perms (increased penetration on the hairline)

8
Alpha hydroxy acids
Indications and results
The results following daily topical application of low concentra-
tions of glycolic acid in a simple aqueous solution start to show
after 2–3 months of continuous treatment, if the concentration is
higher than 8%. Alpha hydroxy acids (AHAs) produce almost
no results after a single application;1 the application has to be
repeated several times to produce clinical results. Whatever the
number of AHA peels, the results for wrinkles, dyschromia, or
photoaging will never compare with the results of a medium or
deep peel (cf. the indications for phenol), except in rare cases
where the dermatological problem being treated is very super-
ficial in origin. The results are not permanent, and biological
analysis shows a return to the original condition 1–2 years after
AHA peels. We must accept these limitations of superficial peels.
AHAs are not toxic to melanocytes, and can therefore be
applied on dark skin and in all seasons, on condition that effec-
tive sun protection is used.2 Contact time (Table 8.1) depends
on skin type, peel concentration and formulation, peel pH, the
method of application, preliminary skin preparation, and other
factors. At an identical pH, a 50% concentration of glycolic acid
will penetrate half as deep as a 70% concentration, and will take
twice as long to do so.
ACNE
The use of AHAs (especially glycolic or lactic acid) in treating
acne has often given good or even excellent results. Easy Phytic
Solution (see Chapter 11) is especially safe, effective, and com-
fortable for this indication. Keratinocyte cohesion in the fol-
licles is also reduced, and this prevents the follicle canals from
closing. AHAs are excellent comedolytics: glycolic acid elimi-
nates the hyperkeratosis responsible for the clogged pores.
After a glycolic acid peel, the top of the lesion will sometimes
whiten to a certain degree as a result of the increase in epider-
mal permeability around the edge of the inflamed lesion. The
whitened areas will disappear in a few days, allowing the seba-
ceous glands to open and drain.
When treating facial acne, concentrations of 50% or more
seem to be the most effective, with contact times of 1–3 min-
utes. Higher concentrations or prolonged contact times cause
unexpected frosting (areas of epidermolysis) and slow down
postpeel healing.
When treating the back, a concentration of 50% is
not enough, and concentrations of 70% should be used for
4–10 minutes. If frosting occurs on the back, it is a sign of greater
effectiveness, in contrast to facial treatment. Maximum effec-
tiveness is achieved when treating active inflammatory acne.
Superficial scars are only rarely and very slightly
improved by repeated AHA peels. Ice-pick acne scars are not an
indication for superficial peels, and deep scars only respond to
a combination of other treatments: dermabrasion, punch eleva-
tion, deep peels, filling, dermal stimulation, or laser. Treatment
of active acne (comedonal, papular, or papulopustular) involves
a combination of skin preparation, weekly sessions of glycolic
acid peels, and appropriate and effective daily cosmetic care
(see Chapter 3). AHAs produce only a cosmetic result and do
not alter the particular genetic traits that lead to acne in some
patients: a peel does not change the blood testosterone level,
the activity of 5α-reductase, receptor sensitivity, or the ten-
dency of the corneocytes to stick together and block the pilose-
baceous units. AHA peels must be accompanied by appropriate
long-term anti-acne daily cosmetic care (Skin Tech’s Purifying
Cream or gel).
AGING OF THE SKIN
AHAs were first used to treat dry skin (hyperkeratinization and
xerosis) before the positive effects on photoaging skin gradu-
ally came to light. Photoaging causes the stratum corneum to
thicken (the skin becomes dry and rough), local proliferation
of melanocytes (lentigines and pigmented hyperkeratosis),
and dermal elastosis (wrinkles, fine lines, and sagging skin).
AHAs can partially help to fight these three types of involution
that progressively and inexorably make the quality of the skin
deteriorate.
AHAs can only provide superficial treatments, whose
direct action is limited to the epidermis. However, for the
careful observer equipped with good photographs, long-term
repetition of AHA peels shows a gradual improvement in the
quality and tone of the skin, which becomes softer and more
even in tone, as well as partial correction of the appearance of
fine lines.3
Contact times can be relatively short when AHAs are
being used to prevent aging, but when the photodamage is
more severe, the length of contact time between the glycolic acid
peel and the skin before neutralization should be increased to
help improve penetration, as sun-damaged skin is more resis-
tant.4 When using glycolic acid creams, the photodamaged skin
soon becomes less dry and rough: results start to show after
3–4 weeks of daily treatment, but obvious clinical results can
be seen more clearly after several months of treatment. Patients
should never be led to expect too much too soon.
Even though patients soon feel an improvement in the
“feel” and quality of their skin, it is pointless to exaggerate
and promise that wrinkles, folds, or fine lines will disappear
altogether: a long series of 50%–70% unbuffered glycolic acid
peels (for 6–12 months) only moderately improves fine lines.
Wrinkles and skin folds are not indications for AHAs. A his-
tological study did not show any significant change after four
monthly AHA peels.5 The long rest period between peels could
be to blame for the lack of histological results, as the peels must
be repeated in relatively close succession to be effective and
benefit from the gradual cumulative effect of the stimulation

Alpha hydroxy acids: INDICATIONS AND RESULTS      53
produced by the different peels. Once a month is too infrequent
and, clinically, weekly repetition is far more effective. Weekly
sessions should be kept up for the first 4–6 weeks of treatment,
if the patient’s skin can tolerate it. Thereafter, peels should be
repeated twice monthly, and eventually once a month as main-
tenance treatment. Treatment for aging skin should, of course,
be accompanied by active daily cosmetic care: DHEA-Phyto,
Actilift, or Renutriv ACE Lipoic Complex.6
Treatment of photoaging is the second preferred indi-
cation for Easy Phytic Solution, and results (tightening effect)
appear rapidly, after the first few sessions.
DYSCHROMIA: MELASMA
Combining glycolic acid in a 50% peel and daily creams of
8%–12% helps moderately improve dyschromia of a purely epi-
dermal origin.
There is relatively little risk of postpeel pigmentary
changes if the peel is applied correctly, but this risk cannot
be ruled out, even when the glycolic acid peel has been kept
in technically perfect conditions (see Figure  37.28). When
treating hyperpigmentation, the skin must be cleansed and
degreased with the utmost care before the peel, because if
the skin is handled too roughly, too much glycolic acid could
penetrate too quickly locally and cause postinflammatory
hyperpigmentation.
Use of an AHA Cream Alone
More often than not, it takes 3–4 months of daily applications
of AHA creams alone to get a clinical result. AHAs are not
renowned for their anti-tyrosinase action; they limit melanin
synthesis mainly through their antioxidant power and increase
the turnover and renewal of cells laden with pigment. Using
AHA creams as the only form of treatment for melasma is
disappointing.
AHA Cream and Peel
Combining regularly applied glycolic acid peels with AHA
daily care creams increases the effectiveness of both. One of
the mechanisms of action of AHAs is to facilitate penetration
of the components of cosmeceutical creams used between the
different peel sessions.
AHA peels help rid the superficial layers of the epider-
mis of an excess of melanin, and AHA creams applied daily
increase keratinocyte turnover, with the melanin produced
being diluted in the increased number of keratinocytes.
Combined use of effective sun protection reduces melanocyte
production and improves the results.
AHA Peels and Non-AHA Cosmetics
Combining regular peels with Blending Bleaching Cream and
effective sun protection (see Chapters 2 and 3) is the most effec-
tive option for treating melasma. Tretinoin can be combined with
other cosmetics, as can hydroquinone, tyrosinase inhibitors, and
antioxidants. It has been proved that applying a depigmenting
cream between peeling sessions is more effective than applying
a glycolic acid cream. It has also been proved that a treatment
combining peels and a depigmenting cream is more effective
than a treatment with depigmenting cream alone.
AHA peels are not, of course, the first choice of treatment
for melasma.
XEROSIS, ICHTHYOSIS, AND WARTS
AHAs have been prescribed for a long time in the treatment
of xerosis, ichthyosis, and sometimes warts. Dry and rough
skin is an excellent indication for AHA creams and peels. Easy
Phytic (see Chapter 11) solution is particularly well tolerated by
patients with ichthyosis, who soon feel an improvement in the
elasticity of the superficial layers of the skin, which pulls less
after the first applications.
HYPERKERATOTIC ECZEMA
Glycolic or lactic acid 15%–20% has been used in the treatment
of hyperkeratotic eczema and hyperkeratosis of the palms and
soles.
GLYCOLIC ACID AS A PREPEEL TREATMENT
Glycolic acid helps to increase penetration and enhances the
action of the active molecules in the cosmeceuticals or medi-
cation applied between peeling sessions. It may act as an anti-
oxidant and chelate iron ions (reducing the production of free
radicals). Applying a 12% glycolic acid cream after exposure
to the sun helps reduce the duration of the erythema. Glycolic
acid has also been used as a preparation for a medium-depth
peel, to enhance the penetration of trichloroacetic acid (TCA) to
the papillary dermis (i.e., before a 35% m/v TCA), for example.
However, in the author’s opinion, the uneven penetration of the
glycolic acid peel is not ideal for enhancing TCA penetration.
The TCA will penetrate more deeply where the glycolic acid
penetrated most, and the overall result could be uneven.
AHA peels have been used unsuccessfully in the treat-
ment of stretch marks, both as monotherapy and in combina-
tion with corundum crystal microdermabrasion before the
peel. Treating the stretch marks with microdermabrasion
beforehand enhances AHA penetration but does so linearly, in
the form of claw marks (Figure 8.1). The results are poor, even
on fine, white, superficial stretch marks.
Figure 8.1  Alpha hydroxy acid peel after microdermabrasion.
Table 8.1  Suggested Contact Times for Glycolic Acid
Condition
Glycolic acid
concentration (%)
Contact time (min)
Acne
50–70
1–3
Keratoses
70
4–8
Fine wrinkles
50–70
4–8
Back
70
4–10

54      Textbook of Chemical Peels
EFFECTIVENESS OF AHA PEELS
The effectiveness, in cosmetic terms, of a glycolic acid peel
can sometimes be miraculous, sometimes non-existent. Some
patients are delighted and others are deeply disappointed, but
more often than not the result of a series of peels with glycolic
acid in an aqueous solution is considered “average.” However,
long repetition of the peels can maintain the appearance of the
skin or even visibly improve it. One clear advantage of glycolic
acid lies in the fact that patients can carry on with their profes-
sional and social lives immediately after the peel, without any
visible signs of flaking7 in the days following the treatment.
Cosmetic improvement is very gradual, and often, if there is no
good-quality pretreatment photographic record, the patient as
well as the practitioner may wonder if the treatment has really
been effective. Although the patient’s immediate entourage
might not really notice any difference, the people the patient
meets less often will notice some change and might comment
on how rested or youthful the patient looks. Repeating peels
over a long period of time ensures the progressive effective-
ness of peels with glycolic acid in an aqueous solution.
Effectiveness Is Doctor-Dependent
The application technique used by the doctor, how carefully he
applies the peel, and his experience are all factors that influence
the outcome of treatment.
Effectiveness Depends on the Galenical Form
Not all glycolic acid peels are the same as far as the skin is
concerned. The peels that are the most difficult to use are gly-
colic acid in simple aqueous solution and glycolic acid masks
(because it is difficult to monitor how the skin is reacting). The
most effective peel would be one that does not need neutral-
izing, in spite of having a pH of 0.5 for a solution with a pKa
between 3 and 4.
Effectiveness Is Doubly Time-Dependent
The effectiveness of a peel with glycolic acid in aqueous solu-
tion depends on the amount of time for which the acid is con-
tact with the skin and therefore on how soon it is neutralized.8
Neutralizing too soon only allows a small proportion of the
acid to act.
Effectiveness also depends on the number of sessions.
The greater the number of sessions, the more visible the
results. The effectiveness of glycolic acid is therefore entirely
dependent on time in both the short and long term. In the short
term, the same concentration will reach the deeper layers if it is
left on longer before being neutralized. In the long term, for the
results to be visible, a number of repeated peels are necessary,
even with 70% unbuffered glycolic acid on a well-prepared
skin. A single application of partially buffered 50% glycolic
acid only allows exfoliation just beneath the surface—plainly
subclinical.
Effectiveness is Patient-Dependent
Preparing the skin properly during the weeks before the peel
helps the glycolic acid penetrate more evenly and deeply.
The quality of the results will be better if the patient follows the
doctor’s recommendations to the letter. Some patients under-
estimate the importance of preparation and do not put on the
creams they have been prescribed. The result is inadequate
and uneven penetration, which leads to inadequate results
and an increased risk of complications. Some overenthusiastic
patients, on the other hand, think they can get into the doctor’s
good books by applying the prepeel treatment more often or
more liberally than prescribed. This results in an unexpected
increase in skin permeability that deepens the effect of the gly-
colic acid and increases the risk of complications, without the
advantage of a better outcome. With Easy Phytic, there should
be no prepeel preparation, as the stratum corneum must be
intact to allow it to act progressively. Creams likely to facilitate
AHA penetration should be stopped 2 weeks before the first
Easy Phytic treatment.
A Glycolic Acid Peel Is Not an End in Itself
A glycolic acid peel should never be considered as an end in
itself but as part of an overall care plan for the past and future
of a patient’s skin. Pre- and postpeel care plays a large part in
the final outcome. For the follow-up, there should be a specially
detailed file recording the various events of the peel and the
treatments accompanying it.
Effectiveness on Wrinkles, Fine Lines, and Folds
A glycolic acid peel is not an effective treatment for folds and
wrinkles. Fine lines can improve gradually over the course of
repeated glycolic acid peels. New collagen synthesis has been
noted in the papillary dermis, but what seems to be responsible
for a large part of the results of a glycolic acid peel on fine lines
is the edema that is caused and maintained by the repeated
application of the acid. The tautening and filling effect on the
skin is sadly only temporary. Whatever the case may be, it is
interesting to note that it is possible to improve fine lines, if
only slightly, without causing skin necrosis. The treatment plan
must be rigorous, and care between and after peels is of vital
importance.
NOTES

1. Except that the skin’s texture may feel smoother.

2. Peyronnet B. Acide trichloracétique ou acide glycolique?
Journal de Médecine Esthétique et de Chirurgie Dermatologique. 1994;
XXI (84): 257–60.

3. Wrinkles can only be improved by using deep peels; folds usu-
ally only respond to surgery, support threads, or fillers. An
improvement in the appearance of fine lines can be seen after
4–6 months of daily application of 10%–12% glycolic acid cream.

4. The stratum corneum is thicker and so more impermeable in
photoaged skin.

5. Piacquadio D, Grove MJ, Dobry M. Efficacy of glycolic acid peels
questioned for photodamaged skin: A pilot study. Dermatology
Times. 1992; May: 52.

6. Skin Tech ().

7. If the glycotic acid is neutralized as soon as erythema appears
and before any frosting appears.

8. In other words, it depends on the “contact time.”

9
Alpha hydroxy acids
Application as cosmetics and as peels
COSMETIC APPLICATION OF GLYCOLIC ACID
Because the application of glycolic acid at first reduces the
thickness of the epidermis, the skin can no longer provide the
same protection against light, and it is essential to use effective
sun protection to avoid the risk of accelerated photoaging. A
glycolic acid cream or gel can easily be prepared in a pharmacy
dispensary, at concentrations of 8%–15%. There are many com-
mercial preparations of glycolic acid that have the combined
advantage of spreading evenly and a galenical form that allows
better penetration of the acid. These low-concentration, daily
topical treatments are mainly indicated for preparing the skin
for other techniques, for follow-up treatment between peels, or
for maintenance treatment afterward. In general, patients who
use glycolic acid as a cosmetic do not expect or will not accept
any flaking. If the skin does flake, treatment should be stopped
and started again a few days later at a lower concentration (or
warm water can be sprayed on the face before applying the gly-
cotic acid cream to dilute it).
As monotherapy, 8%–15% gels (which can be buffered
to the physiological pH to 4.55)1 are applied twice a day, after
washing the face with a mild soap (e.g., Avène®) if the skin is
“normal.” If the skin is dry, care should be taken not to degrease
the skin, so that the gel does not penetrate too deeply. If the
skin is oily and/or acneic, it should be degreased with a glycolic
acid–based cleanser before applying the gel. It is essential to
use effective sun protection.
As a precaution, the initial concentration of glycolic acid
should not be more than 8% and the gel should be applied every
other day at first. The concentration and frequency of applica-
tion can be increased, depending on the skin’s response and
tolerance. When treating severe photoaging, the concentration
of the glycolic acid should be gradually increased from 8% to
12%, 15%, or possibly 20%.
Alpha hydroxy acids (AHAs) can be applied on the face
as well as the neck, décolletage, hands, forearms, and other
parts of the body. It must be remembered that the skin on the
face is far more permeable than the skin on the limbs or torso.
Combination of AHAs and Tretinoin
Shared Effects
Tretinoin and AHAs act on the epidermis and the dermis.
When used over a long period of time, they both have the fol-
lowing effects:
•
An increase in the overall thickness of the epidermis at the
same time as a decrease in the thickness of the stratum cor-
neum: the skin appears smoother and more hydrated.
•
Increased dermal thickness and new synthesis of collagen
and elastin fibers.
Specific Effects
Retinoids induce neoangiogenesis, whereas AHAs act on the
dermis without necessarily going through a phase of inflam-
matory reaction. We can therefore assume that their combined
effects can produce better results while reducing the inci-
dence of side effects thanks to the use of lower doses of each
of these two potential irritants. For example, if there is resis-
tance to (daily or twice daily) monotherapy with tretinoin2 at
0.1%, applying an 8%–10% glycolic acid gel beforehand helps
the retinoid to penetrate more efficiently. Tretinoin and AHAs
can be applied separately, but they can also be mixed in the
same gel.
If, on the other hand, a patient cannot tolerate a concen-
tration of tretinoin at 0.05%, applying an 8%–10% glycolic acid
cream in the morning will make a tretinoin cream at 0.015%
applied in the evening more effective, while reducing the irrita-
tion caused by the retinoid. These combinations must always
be used under close medical supervision, however, as in dual
therapy, skin reactions can be highly unpredictable and severe
in some patients.
More sensitive skins can be treated as follows:
•
Days 1–15: 8%–10% glycolic acid cream in the morning.
•
Days 15–30: 10%–12% glycolic acid in the morning.
•
Days 30–60: 8%–10% glycolic acid in the morning plus
0.015% tretinoin in the evening.
The doses of each product should be increased gradually
thereafter. If the patient has a tendency to erythema, photosen-
sitivity, or telangiectasias, the glycolic acid should be increased
and the concentration of the tretinoin decreased.
If the patient has thin skin, the tretinoin should be
increased more quickly than the glycolic acid.
Combination of AHAs and Hydroquinone
There is no point in combining hydroquinone and AHAs in
a peel solution, as hydroquinone has a tyrosinase-inhibiting
action that can only establish itself gradually and act on the first
biochemical stages of melanin synthesis.
On the other hand, it is worthwhile combining the two
in the daily treatment of melasma between or after peels.
The pharmacist should be asked to add 3%–8% hydroqui-
none to a water-in-oil cream with an 8%–10% glycolic acid
concentration.
Gels are more active and better tolerated by oily skins,
while the most suitable galenical form for dry skins is cream.
Kojic acid (2%–5%) can also be added gradually to the com-
bined glycolic acid plus hydroquinone formulation to enhance
its action.

56        Textbook of Chemical Peels
Combination of AHAs and Other
Topical Pharmaceuticals
The reduction in corneocyte cohesion caused by AHAs allows
topical preparations containing cortisone, antifungal and anti-
mitotic agents, and so forth to penetrate more easily.
5-Fluorouracil (5-FU) has been widely combined with
glycolic acid in the treatment of severe photoaging. Application
should be “pulsed” to limit the inflammatory reaction caused
by daily application of 5-FU. Glycolic acid 10% should be
applied once or twice a day, while the 5-FU (as a cream with a
concentration of 1%–5%) should only be applied on two consec-
utive days per week, every other week. Actinic keratoses on the
scalp can tolerate a weekly application of 5-FU combined with
glycolic acid. David R. Harris3 reports treating actinic cheili-
tis by applying a Vaseline or silicone ointment containing 5%
glycolic acid and paraffin. This treatment can be deepened by
periodic applications of 5-FU and/or light trichloroacetic acid
(TCA) peels.
AHA peels can be used to treat patients of all skin photo-
types who cannot accept any downtime. Results are, however,
difficult to predict: some patients show a rapid improvement
in the quality and color of the skin, while others do not notice
any cosmetically visible change. The unexpected, though rare,
occurrence of complications always poses a major problem
when a treatment has been guaranteed “not to be noticed by a
third party.”
APPLICATION OF GLYCOLIC ACID PEELS
Prepeel Preparation
Table 9.1 lists steps for preparing for glycolic acid peels.
Desquamation
Buffered solutions of glycolic acid, when applied correctly,
only produce virtual desquamation. Water-based glycolic
acid does not penetrate evenly, and the risk of localized
overpeeling, scabbing, or postinflammatory hyperpigmenta-
tion is not insignificant.
The destruction of the epidermis that causes visible flak-
ing depends on how the peel is applied, as well as on the type
of peel used. A short contact time with a 50% glycolic acid peel
at pH 3.5 produces almost no visible flaking, while a longer con-
tact time with 70% glycolic acid at pH 0.5 induces epidermolysis
and the appearance of small scabs and visible flaking. The cor-
rect contact time with a water-based 70% glycolic acid at pH 0.54
causes little or no flaking, but repeating it too soon could trig-
ger visible flaking. Applying a water-based 70% glycolic acid
peel at pH 0.5 with a flat brush will cause less flaking than if
it is applied with a gauze pad (which is slightly abrasive) after
the skin has been disinfected with alcohol or degreased with
acetone or ether, or after the skin has been prepared for several
weeks with tretinoin cream. All other conditions being equal,
applying a greater quantity of AHA causes more of the epider-
mis to be destroyed and more visible flaking.
Easy Phytic Solution, in spite of its pH of 0.5, causes
almost no flaking and penetrates more evenly than other AHAs
because of its formulation and application procedure.
Treating the Face or Body
AHA peels primarily have been used to treat the face but can also
be used to treat other areas of the body. Facial skin is more perme-
able to AHA peels than the skin on the rest of the body. The neck,
décolletage, hands, and forearms can be treated with a combina-
tion of AHA peels and effective postpeel care (see Chapter 3).
With these body treatments, we can expect an improve-
ment in the quality of the structure of the skin, improved
hydration, and some temporary lightening of the complexion.
Lentigines and keratoses should be treated by another
method in parallel with AHA peels. There are other, more
efficient, techniques to treat these problems: liquid nitrogen,
dry ice, Only Touch peel, intense pulsed light (IPL), laser,
Table 9.1  Preparation for Glycolic Acid Peels
Long-term preparation
starts 4–6 weeks before
a water-based AHA peel.
It can be nonspecific or specific. It is not essential, but noticeably improves results by ensuring deeper and
more even penetration of the glycolic acid peel. Greater vigilance is required when applying the peel,
however, as it must be neutralized more quickly.
Nonspecific preparation
to make a water-based
AHA peel deeper and
more even
In the evening, a 0.05% tretinoin cream should be applied (see Chapter 2).
This cream reduces the thickness of the stratum corneum and provides a deeper peel with the same
concentration. A 10% (nonphotosensitizing) glycolic acid gel could be applied on younger women in the
morning.
Specific preparation: to
give patients a focused
care plan
Preparing a patient who has acne is not the same as preparing a patient with photoaging or melasma.
Hyperpigmentation of all sorts responds extremely well to prepeel treatments.
Menopausal or postmenopausal women can benefit from a hormone cream as part of antiaging treatment.
The following formulation can be prescribed:
• Testosterone propionate 100 mg
• Estrone
5 mg
• Estradiol benzoate
5 mg
• Eucerin O/W
45 g
• or Neribase

45 g
See Chapter 2 for more details.
Medium-term preparation
starts 2–4 weeks
before a peel.
This concerns combined treatments used before the peels as well as the cosmeceuticals or pharmaceutical
products used by the patient (see above).
Folds, wrinkles, and fine lines should be treated beforehand with dermal fillers, thread lifts, mesotherapy,
stimulation, or other treatment chosen by the doctor. Benign tumors can be excised or treated by shave
biopsy or lasers. Rosacea and seborrheic dermatitis should be treated before the peel during this same
period. Botulinum toxin ideally should be injected 8 days before the first water-based glycolic acid peel.
Short-term preparation
It is preferable not to put on any cream that could permeabilize the skin nor use any technique likely to
damage the stratum corneum during the few days before an AHA peel. Small retention cysts can be
removed with a needle or number 11 scalpel blade 1 week before applying the water-based glycolic acid.

Alpha hydroxy acids: APPLICATION AS COSMETICS AND AS PEELS        57
and others. Dr. Robert Vergereau (France) compared the use of
dry ice, Erbium laser, Q-switched laser, coagulation, and Only
Touch peel. He concluded that “If all these methods are satis-
factory, in my opinion, the technique using trichloroacetic acid5
is the most beneficial.”
Treatment of other areas of the body with AHAs is not
often described because of the poor penetration of these acids
through the skin of the body. A technique combining abrasion
and an application of Easy Phytic solution (see Chapter 11) is
more successful on the legs, arms, and torso.
Buffered or Unbuffered AHAs?
The results produced by buffered AHA peels can, in a way, be
compared to those produced by unbuffered peels, but only when
applied over a longer period of time and more frequently. From
a histological point of view, all peels produce comparable results
depending on the strength of the peel. The action of an AHA peel
with a pH higher than its pKa and close to the skin’s physiologi-
cal pH (4.5–6) is very slow. A buffered solution will often only be
applied for the first “reconnaissance” peels or on sensitive skins.
Thereafter, the peels will be performed with 70% unbuffered gly-
colic acid solution in a gel or Easy Phytic solution.
How Many Sessions Should Be Anticipated?
AHA peels should be considered a long-term treatment. No
noticeably visible improvement, except for softer skin, should
be expected until after many sessions.
Sometimes, the results do not become obvious until after
8–10 sessions of water-based unbuffered 70% glycolic acid peels.
How frequently the sessions should be repeated depends on
how the skin reacts or how sensitive it is. Some thin and sensi-
tive skins will not tolerate more than one session every 2 weeks,
whereas thicker or oilier skins will easily tolerate a weekly ses-
sion or even more. It is clearly difficult for people who can only
tolerate one session a month to achieve visible results. Even the
most willing patients can be worn down by the boredom of
repeated sessions that can sometimes be unpleasant and have a
limited effect. Patients who cannot be treated more than once a
month often give up treatment long before it has finished.
Classic Application Technique for Glycolic Acid
A glycolic acid peel can be applied in an aqueous solution or
in a gel, with a gauze pad, a brush, presoaked cotton swabs
or pads, gloved fingers, and so on. Compact and opaque AHA
masks have been used, but monitoring the skin while the mask
is on is neither easy nor certain.
The glycolic acid solution is applied quickly (in 15–20
seconds maximum) so that the contact time is the same for the
whole face. The solution should be applied to the most resis-
tant areas first (the forehead) and to the more sensitive areas last
(the eyelids). It is important to develop application habits and
always use the same system, both for applying and neutralizing
the peel.
Partially squeezing out the applicator before using
it guards against the product forming “pools” on the skin.
Massaging the skin with a gloved finger allows more even
penetration or deeper local penetration if the doctor considers
it necessary. By closely monitoring changes in skin color, the
AHA solution can be neutralized before any frosting occurs. To
a certain degree, the contact time is more important than the
total quantity of AHAs applied to the skin: a low overall quan-
tity of glycolic acid left to act for a longer time can penetrate
the skin more deeply than a larger quantity that is neutralized
immediately. As well as the choice of peel, monitoring the con-
tact time is an essential part of any glycolic acid peel. This is
why the glycolic acid peel has been called “time-dependent,”
prompting the purchase of many completely redundant timers.
Glycolic acid can be applied up to a few millimeters from
the eyelashes, no matter what its concentration. If any glycolic
acid comes into contact with the eyes, they should be rinsed
immediately with plenty of water, and drops of artificial tears or
physiological solution should be applied. Glycolic acid is not a
protein coagulant like TCA or phenol, and the risk of damage to
the eye after contact is not high. In fact, dilution from teardrops
appears to be enough to avert most of the danger. The author
has never come across any objective ocular damage, even in
the extremely rare case of contact between glycolic acid and the
eyes. Sometimes, a very small quantity of glycolic acid can be
drawn up into the eye by capillarity if the peel is applied too
close to the conjunctivae. This immediately causes the forma-
tion of tears, which dilute the acid and reduce its aggressiveness.
Patients should be asked to keep their eyes shut while waiting
to have eye drops put in that will bring immediate relief.
CONTACT TIME
The contact time is the time during which the AHA is left to
act before being neutralized and stopping its effect. It depends
more on the appearance of erythema than on the concentration,
the pH, the total volume applied, the number of applications,
and other factors. AHAs in aqueous solution do not penetrate
the epidermis evenly, and the erythema, which is the first sign
of the skin reacting to a peel (Table 9.2), does not appear evenly
either, but rather in spots or patches. It is therefore essential for
the doctor to stay beside the patient during this phase of the peel
and not to take his eyes off the treated area. The safety limits are
not very flexible when using AHA in aqueous solution, and a
peel can go from “too superficial” to “too deep”6 very quickly.
Contact time should end as soon as erythema begins. The
problem is that it is not long before erythema turns to frosting,
and the doctor is often faced with the following dilemma: neu-
tralize too soon and have limited results, or try to neutralize a
bit later and risk complications. It was to avoid this dilemma
that the author developed Easy Phytic solution.
Contact Time for a Glycolic Acid Peel
Each patient’s skin reactivity should be tested by an initial
application of a less concentrated and/or a partially neutral-
ized peel (e.g., 50% at pH 3.5). As a precaution, the initial con-
tact times should be short, to test the skin’s reactivity. When
we say that an AHA peel is “time-dependent,” we mean that
the contact time depends on examining the skin directly and
not on the clock. We do not need to know exactly how long the
product should be left to act: the right contact time is enough
time for erythema to occur, but no frosting. Table 9.3 shows, as
an approximate guide, the depths reached by unbuffered 70%
Table 9.2  Correlation between Skin Appearance and Depth of
AHA Peel
No erythema
Virtual peeling effect
Spots of erythema
Very, very superficial
Patches of erythema
Very superficial
Widespread erythema
Superficial peel, suitable depth for AHAs
Frosting
Too deep for an AHA peel

58        Textbook of Chemical Peels
glycolic acid (pH 0.5) with different contact times on the face.
Doctors must remember, however, that AHAs should never be
used to do anything other an epidermal peel.
Each patient has his or her own particular level of sensi-
tivity and contact time. It is therefore important to take precise
notes on the treatment given: the type of solution, the concen-
tration used, the contact time (except in the case of Easy Phytic
solution, which does not need neutralizing; Figure  9.1), the
places where erythema first appears,7 the number of coats, the
type of neutralizing solution applied, and so forth. These notes
will be useful for determining any potential change in contact
time for subsequent peels. A cautious contact time of 2 minutes
for a first peel with 70% glycolic acid, pH 0.5, on a patient with
healthy skin of normal thickness can gradually be prolonged
by 30–60 seconds in subsequent peels, if the skin can tolerate
it—that is to say as long as there is no frosting.
NEUTRALIZATION
An AHA peel should be neutralized as soon as erythema
appears and before (or, at the very latest, just as) the first pin-
points of protein coagulation (frosting) appear. The peel can be
neutralized with a solution saturated with sodium bicarbonate,
for example. (Sodium bicarbonate is readily available at phar-
macies.) The “bicarbonate system” is a natural and powerful
system for neutralizing organic acids. Neutralizing an AHA
peel with a bicarbonate solution immediately stops its action.
The reaction of an acid with a base produces a salt that has no
peeling activity. The question is then what proportion of acid
was effective during the AHA peel. If unbuffered 70% glycolic
acid is applied and neutralized after a few minutes’ contact
time, what is the proportion of free acid that will have been
effective: 30% or 50%?
If a solution is applied with a concentration of 70% but
buffered at exactly pH 3.83 (which is the pKa of any glycolic acid
solution), it contains only 50% free and active glycolic acid; the
other 50% consists of an inactive salt. In reality, this solution
corresponds to only 50% of the 70%, that is, 35% of pure glycolic
acid. Rapid neutralization of this solution reduces its effective-
ness even further (Figure 9.2).
The problem with AHA peels clearly lies in the neutral-
ization. Easy Phytic provides a solution to this difficult prob-
lem because in spite of its pH of 0.5, this peel does not need to
be neutralized and therefore benefits from the effectiveness of
100% of the molecules applied to the skin.
It should be remembered that rinsing with pure water
dilutes an acid (lowers its concentration), whereas a base solu-
tion neutralizes it (raises its pH). The neutralizing solution
should be prepared before the peel so that it is instantly avail-
able when neutralization is necessary (Box 9.1). Skin burns as
a result of neutralizing too late because of lack of preliminary
preparation of the neutralizer are always considered as profes-
sional misconduct by an expert.
The doctor and assistant should carefully monitor all the
areas treated with acid. Surfaces that develop any local ery-
thema should be neutralized there and then with the tip of a
sponge soaked in saturated bicarbonate solution.
It is possible to apply corticosteroid cream to the local-
ized erythema. When several areas have become erythematous
and been neutralized, the whole face should be neutralized by
applying strips of paper, for example,8 soaked in the neutral-
izing bicarbonate solution (Figure 9.4). If the glycolic acid is
Table 9.3  Depths Reached by Unbuffered 70% Glycotic Acid
(pH 0.5) as a Function of Contact Time
Contact time (min)
Depth of effect
1–5
Gradually deepening epidermolysis, depending
on contact time and skin sensitivity
5
The acid reaches the dermoepidermal junction
10
The acid reaches the dermis, which is not
desirable, as its effect, locally, will be similar
to that of 30–35% TCA m/v
15
The depth of skin necrosis, locally, is
histologically comparable to or greater than
that reached with 35–40% TCA m/v
pH 7,5–8
pH 5.5
pH <2
Cleanser Skin
Tech pH 5.5
Peeling solution
Self neutralization
Skin buffer potential
Physiologic pH
Peeling pH
Physiologic pH
Easy Phytic Solution: Self Neutralizing
Figure 9.1  Easy Phytic Solution is self-neutralizing.

Alpha hydroxy acids: APPLICATION AS COSMETICS AND AS PEELS        59
not completely neutralized, applying a solution of sodium
bicarbonate triggers a chemical reaction that produces a
warm tingling sensation and may contribute to the develop-
ment of temporary postneutralization erythema together with
bubbles. The skin is completely neutralized when no more
“bubbles” are felt. Neutralizing with a bicarbonate solution,
or any other commercial neutralizing solution, is only obliga-
tory when using unbuffered solutions. When the pH is close
to the physiological limits (pH > 4), thoroughly rinsing with
running water is enough,9 because the relatively high pH of
these partially buffered solutions is not too aggressive for the
skin, and diluting the acid is all that is needed to increase its
pH sufficiently.
AHAs are the only peels where neutralization is impor-
tant—TCA, resorcinol, salicylic acid, and phenol do not need
neutralizing.
Glycolic acid is not a protein coagulant. It does not com-
bine with proteins and is not neutralized, like TCA. It remains
aggressive until it is neutralized, diluted, or picked up by the
skin’s buffer systems. After neutralization, the patient may
continue to feel the acid burning in places. The patient can be
given a cotton pad soaked in bicarbonate solution and asked to
neutralize the more sensitive areas more thoroughly until the
burning sensation has completely gone. The patient will often
apply the solution to the nostrils and eyebrows several times.
More sensitive areas can be protected before the peel with
Vaseline applied on a cotton bud.
BOX 9.1  Preparing the Neutralizing Solution
The simplest neutralizing solution consists of a solution
saturated with sodium bicarbonate: Fill a bowl with warm
water and gradually add the sodium bicarbonate powder
(Figure 9.3a), stirring all the time. When the sodium bicar-
bonate no longer dissolves and forms a sediment in the bot-
tom of the bowl, the solution is saturated (Figure 9.3b). There
is no point trying to get a more concentrated solution.
pH 7.5–8
pH 5.5
pH <2
Skin
native pH
Peeling
solution
Peeling pH
Neutralization pH
Glycolic acid peel: pH variations
Peeling
solution
Neutralizer
Figure 9.2  Glycolic acid peel: pH variations.
(b)
(a)
Figure 9.3  (a) Sodium bicarbonate powder. (b) Saturated solution of sodium bicarbonate.

60        Textbook of Chemical Peels
Neutralizing Partially Buffered Solutions
A (partially) buffered solution has an artificially high pH that
makes it less aggressive. In fact, to allow doctors to do their job
properly, the pH of glycolic acid or other AHA solutions should
be given on the bottle. When using a prescription solution from
a pharmacy dispensary, it is vital for the doctor to check the pH
of each solution himself (with a pH test strip, pH meter, etc.).
Checking the pH personally can sometimes bring surprises—
and confirms the need to do so. In case of doubt or if the pH
is not known, it is, in any event, better to opt for neutraliza-
tion: there is no danger in neutralizing a peel, whereas it can be
disastrous not to (Table 9.4). In the interests of caution, it is best
to neutralize the peel in the face of any doubt. After neutraliza-
tion, spraying the skin with warm water gets rid of any excess
bicarbonate, and the face can then be dried.
Neutralizing AHA Peel with a
Versicolor Neutralizer
Recently, Skin Tech launched a new peeling system called Easy
Droxy Complex Peel and Neutralizer Versicolor. This system con-
sists of a liquid crystal gel peeling solution and a patented neu-
tralization cream based on sodium carbonate and basic amino
acids.
The peeling solution is a thick gel that can be applied
using a brush, without running on the skin. It is a hybrid peel-
ing solution that contains different types of acids:.
•
AHAs (glycolic, lactic): superficial peeling and antioxidants.
•
Tricarboxylic acid (citric acid): superficial peeling and ener-
gizer: Krebs cycle, citrate cycle.
•
Beta hydroxy acid (salicylic acid = phenolic acid): bacteri-
cidal, disinfectant, keratolytic, and anti-inflammatory.
•
Pyrone (kojic acid): antipigmentation, disinfectant, cupper
chelator.
See Table 9.5 for more information.
The Neutralizer Versicolor cream is naturally blue and
turns yellow when the skin is acid, turns green when the skin
is at pH:7, and returns to blue when the skin has been totally
neutralized, presenting a pH higher than 7 (Figures 9.5 and 9.6).
POSTPEEL CARE
Further information on care following a peel is available in
Chapter 3.
Immediate Postpeel Care
The appearance of uniform erythema indicates that the glycolic
acid has penetrated properly and is the signal for neutraliza-
tion. After neutralization, spraying with warm water cleans the
skin of any residual chemicals.
Immediately after the glycolic acid peel, the skin is very
permeable, and products applied to it during this period will
penetrate more deeply and thoroughly. This is an ideal time
to apply the classic postpeel care treatments; see Table  3.1 in
Chapter 3.
Care between Peels
Glycolic acid peels help cosmetic or medical treatments applied
between peeling sessions to penetrate more easily.
Tretinoin should be used carefully during the days imme-
diately following a peel, especially when the skin is thin and
dry. The choice of vehicle should be discussed with patients:
a patient with oily skin will not always like using creams and
might prefer a gel; the same gel would be unpleasant for a
patient with thin, dry skin.
Table 9.5  Acids in Hybrid Peeling Solution
Type of acid
Name
Acidity potential
Alpha hydroxy acids
Glycolic acid
pKa: 3.83
Lactic acid
pKa: 3.86
Beta hydroxy acid
Salicylic acid
pKa 2.97
Tricarboxylic acid
Citric acid
pKa1: 3.14
pKa2: 4.75
pKa3: 6.39
Pyrone derivative
Kojic acid
pKa: 9.40
Table 9.4  Neutralization of Glycotic Acid Peels: Appropriate Guide
pH of peel
Procedure
>3.5
Rinse with water
0.5–3.5
Neutralize, then rinse with warm water
(a)
(b)
Figure 9.4  (a) Soaking paper strips in the bicarbonate saturated solution. (b) Application of paper strips.

Alpha hydroxy acids: APPLICATION AS COSMETICS AND AS PEELS        61
pH 7.5–8
pH 5.5
pH <2
Cleanser Skin
Tech pH 5.5
Peeling
solution
Neutralizer
versicolor
Cleanser Skin
Tech pH 5.5
Physiologic pH
Physiologic pH
Peeling pH
Neutralizer
yellow
Neutralizer
green
Neutralizer
blue
Neutralization pH
Easy Droxy Complex Peel: Neutralizer Versicolor
Figure 9.5  Easy Droxy Complex Peel and Neutralizer Versicolor.
Figure 9.6  Overview of application and neutralization process for Easy Droxy Complex Peel and Neutralizer Versicolor.
1.
Skin cleansing. Remove makeup and cleanse the skin using Skin Tech Cleanser pH 5 Foam; rinse
and dry.
2.
Easy Droxy peel application, first coat: Apply peel on the skin. Redness → Apply Neutralizer Versicolor.
No redness → Leave peel 2–3 minutes and apply second coat.
3.
Application, second coat: repeat as for first coat.                                      (Continued)

62        Textbook of Chemical Peels
Maintaining the Results after Peels
When it comes to the patient’s overall treatment plan, he or she will
often ask how best to maintain or improve the results achieved. A
monthly maintenance peel can be recommended, as well as con-
tinued use of the treatment started between peels. Sun protection
is indicated in all cases to limit UV penetration through tempo-
rarily thinned and hyperpermeable skin. See Chapter 3.
NOTES

1. See comments on buffering AHAs later in this chapter.

2. Resistance to tretinoin: no visible signs and no discomfort, even
with relatively high doses; there is no erythema and no unpleas-
ant sensation in the skin.

3. Harris DR. Treatment of Aging Skin with Glycolic Acid. In: Elson
ML (Ed.). Evaluation and Treatment of the Aging Face. New York:
Springer-Verlag, 1995: 31.

4. Effective neutralization as soon as erythema appears.

5. Author’s note: The comparison was made using the Only Touch
peel combined with Easy TCA.

6. That is, too deep in relation to the peel used: a glycolic acid peel
should be superficial.

7. During the next peel, the AHA should be applied last on the
areas where erythema appeared soonest.

8. Cotton pads or any other means of application can also be used.

9. When rinsing with a lot of water, a drop of acid can come into
contact with the eye.
Figure 9.6 (Continued)  Overview of application and neutralization process for Easy Droxy Complex Peel and Neutralizer Versicolor.
4.
Neutralizer Versicolor application, first coat: Quickly apply a uniform coat of Neutralizer Versicolor.
The contact between emulsion and the peeling induces: local thermal reaction, small bubbles, and change
of emulsion color. Remove residue using a cotton disk. Apply second coat of Neutralizer Versicolor.
5.
Neutralizer Versicolor application, second coat: Neutralizer Versicolor allows visual control of the peeling
neutralization in real time.

Yellow color → peeling is not neutralized.

Green and blue colors → peeling is neutralized.

Application can be repeated as many times as necessary to obtain blue color.
6.
Leave Neutralizer Versicolor on the skin for 5 minutes for an optimal moisturizing and calming effect.
Remove remaining residue from the skin. Apply sun protection: Skin Tech Melablock-HSP SPF 30 or
50+. Recommendation: Repeat once a week; 5–10 sessions can be enough for an optimal result.

10
Alpha hydroxy acids
Side effects of AHAs
Complications from alpha hydroxy acid (AHA) peels are rare,
easily avoided, and often spontaneously reversible or treat-
able by simple topical applications. More details on complica-
tions, their origins, prevention, and treatment can be found in
Chapter 37.
ALLERGIES
The author is not aware of any documented case of allergy to
glycolic acid or other AHAs. In the case of an allergic reaction,
the doctor should test for allergies to the solvents or additives
in the AHA solution. Some allergic-type reactions are, in fact,
caused by the AHA penetrating the dermis, which triggers a
limited and localized inflammatory reaction whose symptoms
are redness and swelling. This reaction disappears without
treatment within 48 hours.
PAIN
There may be some irritation and a burning sensation, espe-
cially at the beginning of treatment. Even AHA creams (or
especially gels) can cause irritation at the start of treatment.
The more the skin has been “prepared” or the thinner it is, the
more painful it will feel when the peel is applied. The pain is
proportional to the concentration of the acid and inversely pro-
portional to the pH. A 70% peel is more painful than a 50% peel.
A 50% peel at pH 3.5 is not as painful as a peel at pH 1.5. A 70%
unbuffered solution applied to thin skin prepared with treti-
noin will be more painful than a 50% solution at pH 4 applied
to oily, unprepared skin. Whatever the case, this pain—a kind
of tingling or burning sensation—is quite bearable. There is no
need for anesthesia, analgesia, or nerve blocks. More nervous
patients might appreciate having their faces fanned (with an
electric or handheld fan) or the calming effect of a voice during
the peel. Neutralizing the peel with sodium bicarbonate solu-
tion stops the pain.
ERYTHEMA
The skin must be neutralized as soon as erythema appears. At
the end of the peel, after neutralizing, the skin is usually pale
pink; this coloring lasts between 15 and 60 minutes. Solutions
that are too highly concentrated or are left on too long and
allowed to penetrate too deeply locally can cause the forma-
tion of scabs, which, if pulled off, leave persistent erythema for
several weeks or months. This eventually resolves naturally
and leaves the skin a little softer. It is best to increase concen-
trations and contact times gradually with patients whose pro-
fessional lives will not allow them to spend time locked away
recovering.
TELANGIECTASIAS
Although there is evidence of a certain degree of angiogenesis
with AHAs, telangiectasias are rare.
DRYNESS, DESQUAMATION, SENSITIZATION
Long-term topical use of 8%–15% glycolic acid creams gradually
reduces corneocyte cohesion and can cause the skin to flake.
This effect is not as pronounced as with tretinoin. Dampening
the skin before applying the cream dilutes the product and
reduces the risk of skin sensitization. Daily use of progressively
higher concentrations of AHAs can, however, cause continuous
lysis of the corneodesmosomes and permeabilization—a long-
term thinning of the epidermis. Patients may then complain
that their skin is getting more and more sensitive. However,
some histological studies show that the skin thickens with
long-term treatment with AHAs.
HYPERPIGMENTATION
Postinflammatory hyperpigmentation (PIH) is rare after an
AHA peel. It may result from an error in assessment, indica-
tion, or monitoring, but sometimes it can occur suddenly when
a peel has been performed and neutralized correctly. PIH can
be treated. For more details, see Chapter 37.
BACTERIAL OR VIRAL INFECTIONS
Bacterial infections result from scratch lesions or epidermolysis
from overpeeling. Bacterial infections do not occur when using
topical treatments with 8%–15% AHA cream. The incidence of
herpes outbreaks after a glycolic peel has been performed cor-
rectly is no higher than in the untreated population at large. In
instances of overpeeling and epidermolysis, the probability of
a secondary herpes infection increases with the depth of injury.
There is no need for systematic herpes prevention before an
AHA peel, but if a patient is very prone to herpes, it would be
wise to prescribe valaciclovir to be taken before the peel.
SCARRING
A correctly applied glycolic acid peel does not reach the reticular
dermis, and there is therefore no reason for it to cause scarring.
The author has never come across any cases of scarring after a
glycolic peel, no matter what skin preparation or concentration
of acid has been used. It is obvious, though, that a combination
of technical errors can result in a cosmetic disaster. Applying
70% unbuffered glycolic acid in multiple coats with a gauze pad
pressed firmly onto a thin and dry skin that has been irritated
by a strong dose of tretinoin, without constant monitoring and
diluting simply in water instead of neutralizing with sodium

64      Textbook of Chemical Peels
bicarbonate, could seriously damage the skin and produce
unsightly scars. Any danger of scarring can be avoided by neu-
tralizing areas of local erythema with sodium bicarbonate solu-
tion and not allowing any frosting to occur. If the texture of the
skin should become uneven as a result of particularly uneven
penetration, it can be evened out in the course of later peels.
SHINY SKIN
The effect of AHAs on corneodesmosomes can cause all the
pores of the skin to unblock and allow all the sebaceous glands
to empty at the same time. The skin will remain shiny until it
is next washed.
ACHROMIA
If the peel penetrates too deeply in a particular place, caus-
ing scabbing and delayed healing, it could lead to total and
irreversible depigmentation that, fortunately, is limited to
the surface area of the scab. It is a rare complication of AHA
peels.

11
Alpha hydroxy acids
A new slow-release AHA complex with no neutralization required
GENERAL REMARKS
Since the 1980s, alpha hydroxy acids (AHAs; Figure 11.1) have
been used alone or in combination with other acids with a
view to achieving good cosmetic results, locally or generally,
temporarily or permanently, and without running the risks of
deeper peels. The natural origins of the first AHAs—fruit or
dairy extracts—account for much of their resounding success.
How could anyone resist such a benign-sounding name as “fruit
acids”? The AHA most often used is without doubt glycolic acid,
a small molecule with a low molecular weight that has no dif-
ficulty penetrating the stratum corneum, where it acts as a “cor-
neodesmosome chainsaw.” It was for this property that it was
first indicated in the treatment of ichthyosis and other disorders
involving hyperkeratinization. An AHA applied to clean and
degreased skin breaks down the protein structures that form
corneodesmosomes. The superficial cell layers are then shed
from the epidermis. The skin immediately feels more hydrated,
as the fingers no longer touch the dead and dehydrated corneo-
cytes that have been shed but rather living and well-hydrated
keratinocytes. AHAs are not toxic to melanocytes and can
therefore be applied on all skin types. They can also be used
at any time of the year, on condition that they are combined
with a strong sunscreen. AHA peels have other advantages as
well: they are nontoxic and hypoallergenic, do not cause protein
coagulation, have an excellent safety record, are easy to use, and
produce satisfactory results in a variety of indications.
There is one sizeable cloud on this bright horizon, how-
ever: AHAs have to be neutralized at the right moment to limit
their penetration. If they are not neutralized, AHAs will continue
working until they go beyond their desired effect. Neutralizing
too late may cause serious side effects, while neutralizing too
soon makes the peel completely ineffective. Neutralizing the
peel is not the easiest part of the procedure: the action of the
acids has to be stopped when erythema occurs and before the
first pinpoint frosting appears. The moment the AHAs have
to be neutralized comes between two events that are open to
subjective judgment, which increases the degree of risk. Many
doctors will run through the following interior monologue:
“I should have let the product act longer for it to be effective,”
or worse, “I should have neutralized the AHAs much earlier,
because now there are going to be complications and unwanted
reactions after the peel.” With the second scenario comes a long
period of uncertainty for the doctor, sleepless nights and early
mornings filled with anxiety, because complications resulting
from neutralizing AHAs too late can only be treated slowly and
gradually, sometimes taking several months.
The problems raised by neutralization are well known,
and various solutions have been suggested to minimize the
danger and risk involved with neutralizing conventional AHAs
too late. Partially neutralized, less aggressive AHAs with a pH
of between 3.5 and 5 can be found on the market. These acid
solutions do not need neutralizing, but they do need diluting
with water before any frosting occurs. Less risk, however wel-
come, goes hand in hand with a less effective peel.
Another drawback to having to neutralize conventional
AHAs with a very acid pH is that the effectiveness of an AHA
largely depends on how long the acid is left in contact with the
skin. The longer the contact time, the more active the peel will be.
Hence, there is a temptation to leave an AHA peel to act as long as
possible, in spite of the risk of complications. The aim of neutral-
izing is to stop the effect of the acid. A contact time of just a few
minutes before neutralizing the peel gives it just a few minutes
to be effective. The author therefore aimed to develop a low-pH
formulation—between 0 and 1 for maximum effectiveness—
that does not need neutralizing. Easy Phytic Solution (EPS) was
the first of this new class of low-pH AHAs that are active with
no need for neutralization. Its pH of 0.5–1 (Figure 11.2) is much
lower than the pKa of the different components in the solution,1
which consists mostly of free acid with no ineffective salts.2 Not
having to neutralize the solution also means that there is only
a minor risk of side effects, even when each molecule is left to
achieve its full effect, undisturbed by external neutralization. It
is the skin itself that neutralizes the acids in the EPS.
EPS can therefore be defined as a slow-release AHA solu-
tion for patients who do not want any visible flaking (it is a non-
flaking peel) or for doctors who want to minimize the risk of the
sometimes serious complications of conventional AHAs. The
solution is saponified3 and adjuvanted, and consists of glycolic,
lactic, mandelic, (phenylglycolic) and phytic acids. The peel
solution—which does not need neutralizing—allows the acids
to work gradually and to full effect. This particular property
allows a “bipolar” action: the solution starts working on the
superficial layers of the epidermis, shedding corneocytes in the
same way as conventional AHAs. It then continues working its
way through the skin to reach the deeper layers, slowly and not
too aggressively. The acid molecules gradually lose their effec-
tiveness as they are neutralized by the natural buffer capacity of
the epidermis. The skin can in fact defend itself perfectly well
against acid or base attacks thanks to its buffer capacity, which
is its ability to maintain the homeostasis of its pH as long as the
attack is not disproportionate to its defenses. When its defenses
are overwhelmed by a massive acid or base attack,4 the skin can-
not defend itself, and its proteins are destroyed, denatured, or
coagulated; the skin is “chemically burned.” With EPS, the acid
molecules in the peel solution are stabilized on the surface of the
skin and concentrate in the stratum corneum.5 They are released
slowly and therefore reach the epidermis gradually. This “slow
release” allows the epidermis to use its full buffer capacity to
neutralize the acid molecules that are slowly attacking it.
Unfortunately, there is another significant problem with
water-based AHAs: they do not penetrate evenly.6 They pen-
etrate more quickly in areas where the stratum corneum is

66      Textbook of Chemical Peels
thinner—and therefore more permeable—and more slowly
where the stratum corneum is thicker. They penetrate more
slowly on the oilier6 parts of the face and more quickly where
the skin is dry, infected, or irritated. It is therefore essential to
prepare the skin for 2–3 weeks before the first water-based AHA
peel to even out the thickness of the stratum corneum. The mela-
nocytes also need to be “stabilized” to avoid any potential pig-
mentary changes.
With EPS, the AHAs penetrate far more evenly because
of the type of vehicle used and the slow-release mechanism,
which eliminates the need for prepeel preparation. The differ-
ent types of AHAs used in EPS are important: the three AHAs
in the solution actually penetrate at different speeds. Small mol-
ecules penetrate the skin more rapidly than larger molecules:
the glycolic acid is therefore the first to penetrate, followed by
the lactic acid and finally the mandelic acid, the largest mol-
ecule, which relies on the lytic action of the other acids on the
corneodesmosomes to help it penetrate the skin more easily.
Phytic acid, the other active component in the solution, is
not an AHA. It is a large molecule: inositol hexaphosphoric acid
or cyclohexanehexyl hexaphosphate (Figure 11.3). Because of its
high molecular weight, 660.08, it does not pass easily through
the epidermis. The action of the three AHAs combined with
the phytic acid in the solution, however, makes the stratum cor-
neum more permeable and therefore easier for the phytic acid
to penetrate. Phytic acid is well known for its anti-tyrosinase
and antioxidant action. It is also an iron chelator. This molecule
is therefore a good indication for skin-lightening and antiag-
ing treatments. Finally, phytic acid scavenges the free radicals
BOX 11.1  General Characteristics
of Easy Phytic Solution
4 acids: glycolic + lactic + mandelic + phytic
pH : 0.5–1 [> 60%]
Slow release
Self-neutralizing
Acid = liberation of
H+
Inorganic Acids
(H-x)
Organic Acids
(OH)
-OH (hydroxyl
group): phenol
-COOH
(carboxyl group):
TCA, AHA
Liberation of H+,
used for peelings
H-Cl, dangerous,
not used for
chemical peelings
H+: Proton
Figure 11.1  The AHAs.
HO
OH
P
O
O
HO
HO
P
O
O
O
O
P
OH
OH
OH
OH
O
P
O
O
O
P
OH
HO
O
P
HO
HO
O
Figure 11.3  Phytic acid.
Figure 11.2  Easy Phytic Solution has a pH of 0.5.

Alpha hydroxy acids: A NEW SLOW-RELEASE AHA COMPLEX WITH NO NEUTRALIZATION REQUIRED      67
produced by the inflammation that follows any peel and breaks
the usual vicious cycle of postpeel inflammation:
peel → inflammation7 → vasodilation → O2 intake +
pro-inflammatory components → free-radical production
→ cell damage → self-perpetuating inflammation
→ more free radicals ⇒ vicious cycle established
There are two sides to inflammation. The first is posi-
tive, as it is an essential trigger for postpeel regeneration and
the synthesis of new dermal components—no inflammation,
no repair. The other side is negative, as the combination of
vasodilation (which, among other things, helps improve tissue
oxygenation) and pro-inflammatory components increases the
generation of free radicals that damage the cell structures upon
which the body relies to repair the skin. The presence of phytic
acid, an excellent antioxidant thanks to its 12 hydroxy groups,
could reduce the incidence of postpeel inflammatory reactions.
INDICATIONS
AHAs thicken the epidermis and papillary dermis, increase
the production of mucopolysaccharides, improve the quality of
the elastin produced, and increase collagen density.8 Patients
treated with EPS also describe an appreciable tightening effect.
Although EPS can be used for the same indications as other
AHAs, its two areas of choice are aging and acne. EPS can be
used as a combined treatment or as a maintenance peel with
other deeper treatments; it can also be used alongside other
techniques such as mesotherapy and pulsed light.9 EPS is more
of a stimulating and regenerating treatment than an actual peel,
as there is almost no visible flaking. The epidermis flakes almost
cell by cell and not in “cell plates.” Patients who are reluctant to
have a “peel” for fear of downtime seem to prefer EPS being pre-
sented as a “stimulating solution.” The term superficial peel con-
jures up images of something relatively ineffective that causes
unsightly flaking. EPS can be combined with “mesolift” meso-
therapy to particularly good effect: alternating a mesolift and
EPS every other week would seem to be the best way to proceed.
Aging Skin
Aging skin is an excellent indication for EPS. Note, however,
that it is still a relatively superficial peel and cannot claim to
eliminate folds or wrinkles, which have to be treated by sur-
gery and deep peels or laser treatments. EPS could be called a
“lunchtime peel,” as it can be performed during the lunch hour
and the patient can go back to work immediately.
EPS as a Classic Antiaging Treatment
The classic treatment consists of weekly applications of EPS
together with use of a suitable cosmeceutical cream (see
Chapters 2 and 3,10 and also the section later in this chapter
on application protocol). The total number of peels will vary
between 6 and 10, depending on the skin and how it reacts. At
the end of the active phase of the treatment, a maintenance peel
can be applied once every 2 weeks and eventually once every
month.
EPS Combined with Mesotherapy
A mesolift is a mesotherapy technique that involves inject-
ing stimulating, relaxing, tensing, or filling agents such as
hyaluronic acid, polymerized DNA, vitamins, trace elements,
dimethylaminoethanol (DMAE), eligopeptides, and others into
the dermis. Facial mesotherapy can be rather painful, however,
and may require the use of topical anesthetics such as EMLA.
The side effects are not always invisible; redness, swelling, and
minor bruising may occur.
EPS is therefore ideal for use with a mesolift: mesolift one
week, EPS the week after. It is wiser not to apply EPS immedi-
ately after a mesolift, because the multiple needle perforations
in the dermis and epidermis would enhance local penetration
of the peel solution. Similarly, a mesolift performed imme-
diately after an EPS peel would be extremely painful for the
patient, and the acids in the EPS solution would penetrate
through to the deep dermis. Nevertheless, many European,
American, and Asian doctors have reported using a combina-
tion of EPS + mesolift or mesolift + EPS at the same time, with
excellent results.
EPS Combined with Botulinum Toxin
Ideally, the botulinum toxin should be injected a few days
before the first EPS session. In this way, the two products can
work together to good effect (Figure 11.4). If preferred, the botu-
linum toxin can of course be used after the EPS. If the botu-
linum toxin is injected immediately after the EPS, the needle
will have to go through the nonneutralized acid solution on
the skin and will take a few acid molecules into the dermis,
which will make the injection more painful. It is not known
how botulinum toxin and the AHAs in EPS interact in the body.
The injection could be given, say, a quarter of an hour before the
EPS. Another potential problem is that the postpeel inflamma-
tory reaction—even if minor—could move the toxin. Allowing
a few days between the EPS session and the botulinum toxin
injection would seem to be a wise choice.
(b)
(a)
Figure 11.4  (a) Before treatment with botulinum toxin and EPS. (b) After botulinum toxin and two sessions of EPS.

68      Textbook of Chemical Peels
Handling the skin during the peels and postpeel vasodi-
lation11 does not seem to have much effect on the outcome of the
botulinum toxin injection. In 10 years of experience in injecting
botulinum toxin immediately before applying the trichloroace-
tic acid peel Easy TCA, the author has seen no evidence of any
direct interaction between these two procedures.
Combining EPS and Flashlamp
in Antiaging Treatments
Intense pulsed light (IPL) is a widely used technique for treat-
ing aging skin (Figure 11.5). However, many doctors are disap-
pointed with the results obtained with IPL as a monotherapy
and are looking for a combination of treatments that will bene-
fit their patients. Phototherapy should not be used immediately
after EPS, as the light rays will have a much greater depth of
action, and may cause photochemical reactions. The presence
of EPS on the skin could also refract the pulsed light. EPS can
be used after flashlamp treatment, but it is best to be cautious,
as the energy from the lamp might breach the stratum corneum
and the acids in the EPS might penetrate more quickly.
The doctor should be ready to neutralize the peel at the
least sign of protein coagulation (frosting). It is a good idea to
alternate flashlamp treatment and EPS, as with the mesolift:
EPS one week and flashlamp the following week.
Antiaging Treatment for the Body
EPS does not penetrate body skin as easily as it does facial
skin. Several coats are needed to trigger erythema and large
amounts of solution have to be used. Treating the body with
EPS takes a long time and large quantities of the product. A
combination of sandpaper abrasion and EPS (Figure 11.6) can
be used to treat photoaging on the back and the upper or lower
limbs. Light abrasion12 can thin the stratum corneum enough
to allow the EPS solution to penetrate the skin more easily and
more quickly. The sandpaper should be used gently and evenly,
without causing any unpleasant sensation, pain, or bleeding.
Only the most superficial layer of the stratum corneum
should be removed. Any deeper abrasion that destroys the stra-
tum corneum is to be avoided, as the active components of the
EPS would penetrate the skin too quickly and soon saturate its
defenses, its buffer capacity. When using this abrasive tech-
nique, it is essential to have the necessary equipment at hand to
neutralize the peel (see the section on neutralizing glycolic acid
in Chapter 9) in case it penetrates more deeply than desired.
This technique can be repeated at a minimum of 2-weekly
intervals only.
More Frequent Application
Another application technique for EPS can be considered,
especially for patients with resistant skin who would benefit
from a more intense tightening effect. EPS is applied follow-
ing the usual protocol as described later in this chapter, but
it is repeated more frequently. Applying the solution more
frequently requires great care and experience. Daily appli-
cations of EPS allow the peel to gradually penetrate more
deeply. After a few days, small scabs will start to appear,
signaling that the maximum depth has been reached and
must not be passed. Within about 2 weeks, the scabs will
have healed, and daily applications can be started again.
Appropriate cosmeceuticals should be used between the two
series of daily peels. For quicker results, the EPS can also be
applied two or three times a week (e.g., on Saturday, Monday,
and Wednesday), especially on thick and oily male skin or in
cases of acne.
Antiaging Maintenance Treatment
EPS can be used to maintain the results of other peels when the
patient wants a maintenance treatment without visible flaking.
It should then be applied once a month.
Acne
EPS is an excellent treatment for mild comedonal, papular, or
papulopustular acne. Peels are obviously not indicated in more
severe cases of acne, for which only dermatological treatments
will do. Comedones, microcysts, and “whiteheads” should be
removed13 during the week before the first EPS to avoid han-
dling the skin immediately before the peel at the risk of the
EPS penetrating too deeply. Some doctors report removal of
comedones or microcysts immediately before EPS, with good
results.
EPS can improve the appearance of acneic skin in just a
few sessions when it is combined with Skin Tech’s Purifying
Cream, which consists of glycolic acid, retinol, vitamin E,
Figure 11.5  Sun aging, thinning skin, yellowish color.
Figure 11.6  Day 4 after EPS preceded by superficial abrasion
with 3M Wetordry sandpaper P220.

Alpha hydroxy acids: A NEW SLOW-RELEASE AHA COMPLEX WITH NO NEUTRALIZATION REQUIRED      69
triclosan, glycyrrhetinic acid, and tea-tree oil. As can be seen
in Figure 11.7(a, b) (see also Figure 11.8), four EPS peels used
in conjunction with Purifying Cream can vastly improve a
patient’s pustular acne. After four sessions, the acne is almost
inactive. The oldest postacne pigmentation persisted, however,
and in this case we continued to apply EPS once a week (four
extra sessions), combining it with Blending Bleaching Cream
(containing tyrosinase inhibitors and antioxidants) to treat the
persistent pigmentation. After eight sessions of EPS, of which
the first four were combined with Purifying Cream and the last
four with Blending Bleaching Cream, the patient’s skin started
to look healthier (Figure 11.7c).
Pigmentation Disorders and Other Indications
EPS acts similarly to other AHAs.
UNWANTED EFFECTS: PRECAUTIONS
EPS is a very particular peel and has its own particular side
effect. The day after application, an average of 2% of patients
develop an allergic-type reaction consisting of small, slightly
pruritic pinkish nodules (Figure 11.9). This reaction is only seen
with this peel. It can often result from using products before
a peel that enhance penetration of the acids or from postpeel
treatments that are unnecessarily aggressive or incompatible.
Questioning patients closely about their cosmetic routine may
provide an answer. In most cases, however, it seems to be for
the following reason: in classic AHA peels14 the AHAs have to
be neutralized, but with EPS they are not; as they are not neu-
tralized, the acids may penetrate as far as the dermis and cause
a local inflammatory reaction (a source of fibroblast stimulation
and new collagen production as well) in the “highest” dermal
papillae. This inflammatory reaction subsides by itself within
1–2 days at most. An allergic reaction is also theoretically pos-
sible and should be treated accordingly. That will also disap-
pear within a few days (Box 11.2).
This type of reaction should be seen as purely
­inflammatory—a positive reaction if the inflammation is con-
trolled by antioxidants and does not last more than 2 days. If it
does go on any longer, it could be considered an allergy.
EPS contact with the eyes should be avoided. In the case
of contact, the eyes should be rinsed with artificial tears or
physiological saline solution.
EPS may also, in some cases, penetrate too deeply or too
quickly if the patient has been using skincare products that
thin or remove the stratum corneum. Patients using topical
(a)
(b)
(c)
Figure 11.7  (a) Active papulopustular acne and postacne pigmentation. (b) After four sessions of EPS and Purifying Cream, the acne
has almost disappeared. (c) Substitution of Purifying Cream with Blending Bleaching Cream for PIH treatment.

70      Textbook of Chemical Peels
BOX 11.2  Excessive Penetration
Appearance of an “acne-like” or “allergy-like” reaction some
hours—or the day—after Easy Phytic Solution (EPS) usually
means that for some reason, EPS penetrated the papillary
dermis.

1. Check if prepeel conditioning did not increase acid
penetration.

a. Medical prepeel.

b. Home cosmetics or waxing, scrubbing, and
so on.

2. Check if too much acid has been applied on the
specific skin of this single patient.
Retrospective studies during nearly 20 years of use
show clusters of this side effect, limited to a specific user
and not related with a lot number, season of the year, or skin
type.
Surprisingly, the next peeling usually does not pro-
duce the same side effect. This might be the result of a skin
structure normalization after peeling.
If the side effect has a tendency to increase and not to
decrease during the next hours, the possibility of an allergic
reaction should be studied.
Figure 11.9  A complication that is specific to EPS: an acne-like
reaction that lasts 24–48 hours and subsides by itself, occurring in
an average 2% of patients.
(a)
(b)
(c)
Figure 11.8  (a, b) Papulopustular acne before treatment. (c) After four sessions of EPS and Purifying Cream, the acne is no longer active. After
cleaning active acne, the Purifying Cream should be replaced with Blending Bleaching Cream to get rid of the pigmentation.

Alpha hydroxy acids: A NEW SLOW-RELEASE AHA COMPLEX WITH NO NEUTRALIZATION REQUIRED      71
retinoids, AHA creams, or benzoyl peroxide should stop using
them 2 weeks before EPS to ensure that the stratum corneum
regains its normal thickness and function.
Figure 11.10 shows the results of overpeeling in a young
patient who had been using a benzoyl peroxide cream. Benzoyl
peroxide is a powerful pro-oxidant used in the antibacte-
rial treatment of acne, and it reduces the stratum corneum’s
impermeability properties. The EPS can then penetrate more
deeply into the skin. In this case, a fluorocortisone cream was
applied immediately. Between the second and sixth day, the
patient was showing areas of local erythema that were treated
with topical cortisone. On the 10th day, there were no visible
sequelae.
Other complications caused by AHAs are extremely rare
with EPS. Infection or pigmentation problems are often caused
by errors made when neutralizing AHA peels. EPS is automati-
cally neutralized by the skin’s buffer capacity, and postpeel
complications are far rarer than with conventional AHA peels.
See Box 11.3.
Prepeel Preparation
This is likely to increase the penetration of the acids unnec-
essarily. EPS was designed to avoid any prepeel treatment.
Application of EPS should be delayed for 2 weeks if there
has been any prepeel preparation: EPS uses the stratum cor-
neum as a reservoir for the slow release of the acids, and if it
has been damaged, it can no longer fulfill this role and the
acids will penetrate too rapidly through the thinned layer of
skin. Body skin is much less permeable than face skin. This is
why an abrasive technique has been described earlier in this
chapter.
Cleaning the Skin
Any makeup should be removed and the skin cleansed
twice with Skin Tech Cleanser (foam without glycolic acid
[Figure  11.11]); the skin should then be rinsed with warm
water and dried with a swab. Alcohol or acetone should not be
used before EPS because these products remove surface lipids
and increase skin permeability (which is not necessary with
EPS).
BOX 11.3  Simple Application Protocol
3. Specific cream after peeling
Ex: acne: Purifying Cream
Ex: skin tension: Actilift
2. Apply
Apply the last coat when the patient
expresses a tingling sensation
1. Cleanse
Wash
Dry
Figure 11.10  Abnormally deep penetration in a young patient who
had been applying benzoyl peroxide locally for acne.
Figure 11.11  Prepeel skin cleansing using the prepeel cleanser
foam.

72      Textbook of Chemical Peels
Skin Tech Cleanser has a physiological pH of 5. It allows
the skin to return to a normal pH before applying peeling
solutions.
Application
Small cotton wool balls seem to be the best method of applica-
tion. A syringe is used to draw out 2–2.5 cm3 of the EPS. The
cotton wool ball is soaked (not too much), and the solution is
applied evenly and quickly over the whole face. Two coats are
usually enough to produce a tingling sensation on the skin.
When the patient can feel some tingling, one last coat is applied
with the same applicator. There should be no frosting. In the
case of inadvertent frosting,15 a neutralizing solution of sodium
bicarbonate should be applied immediately.
If there is no frosting, a neutralizing solution should not be
applied—the skin neutralizes EPS automatically. Patients with
very permeable skin may feel some tingling as soon as the
first coat is applied. They should be given a total of two coats
only: the first triggers the tingling and the second finishes
off the peel. Patients with thick skin may not feel anything
before the third coat. They should be given a total of four
coats (Box 11.4).
The treated area should be massaged with a gloved hand
to ensure even penetration until the tingling sensation sub-
sides. Slight tingling is normal and can last from 30–60 minutes
after the application of this slow-release solution.
Immediate Postpeel Period
As soon as the patient says that the tingling has subsided, the
skincare cream best suited to the patient’s skin should be rubbed
in: Purifying Cream in the case of acne, Blending Bleaching
Cream in the case of pigmented marks, DHEA-Phyto cream for
antiaging for patients over 40, and Renutriv ACE with lipoic
acid to prevent aging in patients under 40. Actilift cream with
DMAE can be used to increase skin firmness. These creams
penetrate much more easily immediately after the AHAs have
been applied, but using a plastic occlusive film (Figure 11.12)
for 20–30 minutes further enhances penetration of the skincare
creams.
In vivo, the natural water content of the stratum corneum
is relatively low. When the surface of the skin is occluded with
an impermeable plastic film, the water that normally evapo-
rates through the epidermis (TEWL16) can no longer do so, and
water of endogenous origin gradually soaks the stratum cor-
neum, which can absorb up to 5–6 times its dry weight. The
thickness of the stratum corneum increases in proportion to the
amount of endogenous water absorbed and can become up to
four times thicker.17 It is then far more permeable to the water-
soluble ingredients, and this improved permeability lasts
for several hours after the occlusive film has been removed.
Occlusion raises the temperature of the hyperhydrated epi-
dermis and makes the various hydrophilic ingredients in the
creams more soluble. Finally, occlusion prevents the active
components in the creams from evaporating too quickly. The
plastic film is then removed and any excess cream is rubbed in
to enhance penetration one last time. All of the products—EPS
and cream—are left on the skin until the following morning,
when the patient can wash his or her face.
Postpeel Period (3–4 Days)
The skin flakes only very slightly, usually unseen by the
naked eye, because it practically flakes “cell by cell.” The
skin should be kept fully hydrated with a cream containing
vitamin E but without fruit acids (Vit. E Anti-oxydant), and
the cream most appropriate for the problem under treatment
should continue to be used. This will often be the same cream
applied to the skin immediately after the peel (see Table 3.1
in Chapter 3).
Period between Peels (between
Two EPS Sessions)
The appropriate cream should continue to be used between
peels. Exposure to the sun’s rays must be avoided; this means
staying out of the sun and using an effective sun protection
cream for 2 weeks after the last peel.
Repeating the Peel
When EPS is the main treatment, it can be repeated once or sev-
eral times a week (see earlier discussion). When EPS is used as
a maintenance treatment with other peels, it can be repeated
once or twice a month.
In standard treatment, EPS can be applied once a week for
6–8 weeks. Thereafter, it is applied as a maintenance treatment:
four extra EPS peels, once every 2 weeks. Finally, in the long
term, EPS can be applied once every 4–6 weeks (Figure 11.13).
CONTRAINDICATIONS
•
Women who are pregnant or breast-feeding (as a
precaution).
•
Presence of herpes or other active lesions.
•
Lesions of unknown origin.
•
Allergy to one of the components.
•
Unrealistic hopes.
BOX 11.4  Average Number of EPS Coats
Thin skin:
2
Normal skin: 2–3
Thick skin:
3–4
Figure 11.12  Postpeel occlusion with a suitable cosmeceutical
for a duration of 15–30 minutes.

Alpha hydroxy acids: A NEW SLOW-RELEASE AHA COMPLEX WITH NO NEUTRALIZATION REQUIRED      73
CONCLUSIONS
EPS is the first slow-release AHA peel that does not need neu-
tralizing, in spite of its pH of 0.5–1. This makes it extremely
safe to use. It combines the known superficial peeling effects
of three AHAs with the antioxidant, chelating, and tyrosinase-
inhibiting action of phytic acid (Table 11.1). It is a new type of
peel that overcomes all the problems associated with neutral-
izing conventional AHAs. EPS allows each of the molecules in
the solution to act to full effect, without being neutralized. The
best indications for EPS are the treatment of adolescent acne
and aging skin, on which it has a tightening effect.
NOTES

1. Glycolic acid has a pKa of 3.83, lactic acid a pKa of 3.86, and man-
delic acid a pKa of 3.36.

2. See Chapter 6 for a discussion of pKa.

3. Saponification allows the acids to act more evenly.

4. As is the case when unbuffered peel solutions are applied to the
skin.

5. It is therefore essential for the stratum corneum to be complete
when using EPS. If any preliminary treatments reduce its thick-
ness, the solution may penetrate too quickly and saturate the
skin’s buffer capacity.

6. AHAs are water-soluble.

7. Dolor–Rubor–Tumor–Calor.

8. Ditre CM, Griffin TD, Murphy GF, Sucki H, et al. Effects of
alpha-hydroxy acids on photoaged skin: A pilot clinical, histo-
logic, and ultrastructural study. Journal of the American Academy
of Dermatology. 1996; 34(2 pt 1): 187–95.

9. EPS can be applied after pulsed light treatment, unless the skin
has been made excessively permeable. See the discussion later in
this chapter.
10. Although EPS does not require any specific prepeel care.
11. It should be noted that EPS and Easy TCA are both used in con-
junction with anti-free-radicals that control the postpeel inflam-
matory reaction. This is not the case with the majority of other
peels. The author’s experience is based only on the combination
of botulinum toxin and EPS or Easy TCA. Combinations with
other peels have not been tested.
12. For example, with 3M Wetordry sandpaper P220.
13. Comedone remover, No. 11 scalpel blade, point of a needle.
14. For example, a 70% unbuffered glycolic acid peel.
15. Frosting has rarely been described; the author has never come
across it.
16. Transepidermal water loss: 5–20 g of water/m2 of skin under nor-
mal physiological conditions.
17. The increase in permeability is also due to a reduction in cor-
neocyte cohesion related to the unusual hyperhydration of the
stratum corneum.
Table 11.1  Differences between Obsolete Glycolic Acid Solutions and Easy Phytic Solution
Obsolete glycolic acid peeling solutions
Easy Phytic Solution
Prepeel preparation
Without prepeel preparation
Exclusively hydrophilic solution
Solution hydro + lipophilic
Complexity of protocols (avoid upper eyelid, nostrils, etc.)
Very simple protocol
Random neutralization at time x
Autoneutralization by skin
Neutralization stops the activity of acids
No neutralization, 100% of active acids
Neutralization too early: inefficient
Autoneutralization
Neutralization too late: danger
Autoneutralization
Uncontrolled activity, strong mobility of protons
Partial inactivity of protons
Uncontrolled and massive penetration
Controlled and sequential progressive penetration
pH : often = +/– 3
pH: +/– 1
No reservoir effect
Reservoir effect
—
Reactivation of the acids in the skin
Uncontrolled inflammatory reaction
Controlled inflammatory reaction
Random social life
Social life preserved
Possibly numerous complications
One unique transitory complication described
8 days
7
8 days
7
8 days
7
8 days
7
15 days
7
4–6 weeks
7
Time line
1st EPS
2nd
3rd
4th
5th
6th
7th
Figure 11.13  Diagram of repeated EPS peels.

12
Trichloroacetic acid
General information, toxicity, formulations, and histology
HALOACETIC ACIDS
Haloacetic acids are derivatives of acetic acid in which one or
more hydrogen atoms on the alpha carbon1 are replaced by hal-
ogens (fluorine, chlorine, bromine, or iodine) (Figure 12.1). The
haloacetic acid most commonly used in peels is trichloroacetic
acid, and we will therefore look at the chlorine derivatives of
acetic acid.
Acetic Acid
Acetic acid (Figure 12.2), also known as echanoic acid, has a
low molecular weight of 60.05 and a pKa of 4.76.2 It is obtained
by distilling vinegar (the acetic acid that comes from the action
of certain aerobic bacteria on dilute alcohol) or through the
Monsanto process by the reaction of carbon monoxide with
methanol at high temperature and pressure. It is a strong irri-
tant to the eyes, mucous membranes, and skin. Prolonged con-
tact between the skin and “glacial” acetic acid3 can cause skin
necrosis. Acetic acid has disinfectant and fungicidal properties.
It is not carcinogenic, mutagenic, or teratogenic to animals or
humans. The oral LD50 in rats is 3.310 mg/kg.
Monochloroacetic Acid
Monochloroacetic acid (MCA; Figure 12.3), also known as chlo-
roacetic acid and chloroethanoic acid, has a molecular weight
of 94.5 and can be obtained from the reaction between acetic
acid and chlorine under high pressure. The pH of an 80% MCA
solution is lower than 1 and its pKa is 2.82.
In both its acid form and its salt forms (e.g., sodium
monochloroacetate), MCA is highly toxic to the skeletal mus-
cles, the renal system, and cardiovascular system and is rapidly
absorbed through the skin and mucous membranes.
MCA poisoning by ingestion, inhalation, or exposure of
more than 5% of the body surface area is frequently lethal.
The symptoms of poisoning are not immediate; they can
appear between 1 and 4 hours after exposure. The noncorro-
sive sodium salt does not penetrate the skin and is not toxic
by skin contact (unlike MCA, which passes through the skin
very easily). It is, on the other hand, highly toxic by the oral
route. There are no data available on the parenteral adminis-
tration of MCA in humans. In laboratory animals, however,
an injection is rapidly lethal. MCA accumulates in the liver
and kidneys before it accumulates in the brain. Elimination
of MCA is renal in humans: most of it is eliminated in its free
form, with a small part being eliminated in conjugated form
with glutathione.
The mechanism of MCA toxicity seems to be via inhibi-
tion of the enzyme pyruvate dehydrogenase; this inhibition
blocks the Krebs (tricarboxylic acid) cycle and disrupts the cell’s
energy supply. Almost immediately, the cell finds itself without
energy. Ketoglutarate dehydrogenase activity is also reduced,
which causes lactic acidosis. The MCA also damages the blood–
brain barrier, probably through the formation of vascular endo-
thelial microlesions.
Symptoms of poisoning begin with nausea and vomit-
ing, diarrhea, and central nervous system (CNS) excitation with
disorientation. The effects observed later on or with higher
doses include CNS depression, cerebral edema, severe myocar-
dial depression, coma, and cardiogenic shock resulting from
nonspecific myocardial lesions and significant arrhythmias.
Within the first few hours, severe metabolic acidosis4 with
hypokalemia occurs. The severity of the rhabdomolysis causes
myoglobinuria severe enough to cause kidney failure5 in those
who survive it. One treatment involves administering dichlo-
roacetate by slow (in 10 minutes) intravenous injection (50 mg/
kg), if possible before metabolic acidosis begins. The dichloro-
acetate is only active as long as all the pyruvate and ketoglu-
tarate dehydrogenase molecules have not been deactivated by
the MCA.
The severity of poisoning due to skin contact depends on
the surface area of skin exposed: applying an 80% MCA solu-
tion on less than 5% of the body surface area can cause severe
poisoning, while exposing 6%–10% of the body surface to MCA
is often lethal.
MCA has nevertheless been suggested as a dermatologi-
cal treatment for mosaic warts or periungual warts at a concen-
tration of 80% or 60 g of MCA + 10 ml of water. Treating warts
involves MCA coming into contact with a very limited area of
skin, which explains the absence of poisoning when the treat-
ment is performed carefully. MCA has also been combined with
salicylic acid and is considered more effective than dichloro- or
trichloroacetic acid in the treatment of warts. Because of this
product’s very high and potentially fatal toxicity, its use and
indications should be strictly limited.
Monofluoroacetic acid is even more toxic than MCA,
being fatal after ingested doses of 2 mg/kg, whereas MCA is
fatal after doses of 50 mg/kg.6
Dichloroacetic Acid
Chemistry and Toxicity of DCA
Dichloroacetic acid (DCA; Figure 12.4), also known as bichloro-
acetic acid and dichloroethanoic acid, has a molecular weight of
128.94 and a pKa of 1.3. It is soluble in water, alcohol, and ether.
DCA has been used in the treatment of severe lactic acido-
sis. No clinical side effects have been observed after parenteral
administration. On the contrary, intravenous administration
of DCA during experimental poisoning of rodents with MCA
increased the survival rate, raising it from 8% to 83% after an
injection of 50 mg/kg and from 8% to 100% after an injection of
100 mg/kg. There are strict protocols for the injection of DCA
in the case of MCA poisoning.

Trichloroacetic acid: GENERAL INFORMATION, TOXICITY, FORMULATIONS, AND HISTOLOGY      75
When ingested, DCA is rapidly absorbed by the diges-
tive tract. In animals, only 1%–2% of the quantity ingested is
found in the feces, which means that the acid is almost com-
pletely absorbed. Only 1% is found, in free form, in the urine. In
humans, up to 5% of DCA can be found in the urine, very soon
after DCA has been absorbed. Peak plasma levels are reached
within 15–20 minutes in humans. Intoxication by inhalation is
rare, as DCA is not a very volatile substance.
DCA causes the liver to increase in volume as a result of a
buildup of glycogen. Increases in aminotransferase (transami-
nase) levels have been observed during treatment with high
doses of DCA, in both rodents and humans. DCA can cause
focal, or even widespread, hepatocellular necrosis in mice, but
no cases have been described in rats, dogs, or humans, even
when administered in high doses. Neurological toxicity in
humans is limited to sedation and potential peripheral neu-
ropathy that is reversible.
DCA undergoes oxidative dechlorination that converts it
into glyoxylate,7 which is in turn oxidized into oxalate,8 reduced
into glycolate,9 and eventually transaminated into glycine.10
However, in certain individuals, the DCA can be partially con-
verted into MCA. This has been described in a child suffering
from congenital lactic acidosis. It appears that the DCA may
enhance the development of hepatocellular carcinoma in ani-
mals, although not in humans.11 DCA is genotoxic in vitro and in
vivo and induces DNA hypomethylation in vivo. The oral LD50
in rats is 2.820 mg/kg. The human toxicity of DCA is mainly
local, through chemical burns, but DCA could be considered
to be potentially carcinogenic in humans. To date, there is no
convincing data on this subject.
Application Protocol for DCA
DCA has been shown to stimulate keratinocyte growth and
differentiation in vitro.12 It has been used in the treatment of
human papillomas, without much success,13 as well as in the
treatment of epistaxis.
DCA is used as a cauterizing agent in the treatment of all
types of warts, calluses, corns, xanthelasma, seborrheic kerato-
ses, ingrown toenails, and similar conditions. It is just as effec-
tive as other methods such as electrodessication or dry ice.
DCA is a powerful keratolytic, and it is important to
apply it only to the lesion being treated. Before any treatment,
Vaseline should be applied around the lesion to prevent any
contact with healthy skin. The doctor should also have some
water at hand to wash the skin in case of inadvertent contact.
A neutralizing solution of sodium bicarbonate can also be used
immediately in case of accidental contact with the skin.
The quantity of DCA required largely depends on the
type of lesion being treated. Very thick and horny lesions are
treated using a cotton bud. A wooden toothpick soaked in DCA
solution can also be used; it should be pushed inside the callus
or wart. Three to five applications are necessary to get results
on very thick lesions, whereas only one or sometimes two
applications are enough on relatively flat lesions. The depth
of application is monitored by watching for the appearance of
protein coagulation, which turns the skin a whitish-gray color.
A combination of shave excision and chemical coagulation can
also be used. The top of the wart is first removed with an elec-
trosurgical or radiofrequency knife. The DCA is applied after
the edges of the wart have been protected with a thin layer of
Vaseline. Foot calluses should be pared surgically before the
acid is applied. Posttreatment care consists of covering the skin
with Vaseline to help it flake more quickly. Large calluses often
have to be treated several times. Treating xanthelasma with
DCA is fairly common.14 The skin around the xanthelasma
must be protected with Vaseline and the DCA applied care-
fully and not to excess. The scars are mostly invisible. Treating
xanthelasma with phenol, however, leaves no scarring (see
Chapter 36). The potential toxicity of DCA means that it can-
not be used on a large absorbent surface area. The author has
found no significant references to the use of DCA in full-face
or body peels.
Trichloroacetic Acid (TCA)
Chemistry and Toxicity of TCA
Trichloroacetic acid (Figure 12.5), also known as trichloroetha-
noic acid and trichloromethane carboxylic acid, comes in the
form of colorless or white crystals and has a distinctive sharp,
pungent odor. As far as its toxicity is concerned, industrial acci-
dents have been reported in which individuals were subjected
to high doses of TCA, either by being splashed with the solu-
tion over large areas of the body or by accidental ingestion or
X
Y — Cα — C
Z
—
OH
O
Carboxylic
acid group
Figure 12.1  General chemical structure of a haloacetic acid. α
indicates the alpha carbon atom. X, Y, and Z represent hydrogen (H)
or a halogen (F, Cl, Br or I)—at least one of these must be a halogen.
H
C
C
H
H
O
OH
Figure 12.2  Chemical structure of acetic acid.
H
C
C
H
Cl
O
OH
Figure 12.3  Chemical structure of monochloroacetic acid (MCA).
Cl
C
C
H
Cl
O
OH
Figure 12.4  Chemical structure of dichloroacetic acid (DCA).

76      Textbook of Chemical Peels
inhalation of concentrated vapors. However, such toxicity has
never been described when TCA has been used as a chemical
peel. It is nevertheless worthwhile to become acquainted with
the potential symptoms of industrial poisoning.
TCA is readily absorbed through the respiratory and
digestive tracts. Acute accidental exposure to TCA has caused
skin necrosis. Contact with the eyes causes burns or irritation,
depending on the concentration of the acid. Exposure of the eye
to small amounts of solution with a concentration equal to or
lower than 15% m/m does not appear to cause any irreversible
damage to the cornea. Immediate dilution with physiological
saline solution instantly stops the burning and any risk of dam-
age to the eye. However, the proteins in the cornea could coagu-
late with larger amounts of low-concentration TCA or smaller
amounts of high-concentration TCA.
Inhaling concentrated vapors of TCA can irritate the respi-
ratory tract. Poisoning through inhaling high doses of TCA can
cause headache accompanied by nausea, vomiting, and cough-
ing. Higher concentrations cause weakness, dizziness, bronchi-
tis, and/or pneumonia. Acute poisoning with TCA vapor can
lead to chest pains, breathing difficulties, low blood pressure,
edema of the respiratory tract, suffocation, and death.
Accidental ingestion of TCA causes irritation and burns
in the digestive tract, vomiting, diarrhea, and low blood pres-
sure. Accidental ingestion of high concentrations can erode the
teeth and cause necrosis of the jaw.
Controlled ingestion of 3 mg/kg of TCA in three male
volunteers showed a half-life of 50 hours. Liver toxicity has
been studied in mice: hepatomegaly (30% enlargement) was
observed in male mice given water containing 1 g/l of TCA for
52 weeks. In a group given water with a concentration of 2 g/l
of TCA, the liver enlarged by 63%. The incidence of liver carci-
noma did not increase, irrespective of the administered dose.
In another study, it was proved that TCA does not cause ade-
nomas or liver cell carcinoma, even in rodents pretreated with
ethylnitrosourea, conventionally used to induce carcinomas.
No in vitro studies using human cells have shown any chromo-
somal abnormalities after contact with TCA. To the best of the
author’s knowledge, no studies have shown any link between
chronic exposure to TCA15 and cancer in humans. When TCA
is applied to the skin, it is not absorbed, and it is therefore not
toxic in this application.
AQUEOUS SOLUTIONS OF TCA
Hydrophilicity of TCA Crystals
TCA crystals are very hydrophilic and therefore unstable in
the presence of water. They readily dissolve on exposure to
atmospheric humidity. This extreme hydrophilicity can cause
problems when TCA solutions are made up in a pharmacy. In
fact, the packaging of pure TCA crystals usually allows for the
preparation of far more peel solution than the doctor actually
needs. The pharmacist does not usually dissolve all the crystals
at one time, as this would produce a large quantity of solution
that is difficult to store. He or she will usually measure out
the quantity of crystals needed for each order of peel solution.
Every time the bottle is opened and every time the pure TCA
crystals are taken out, they come into contact with atmospheric
water, which gradually hydrates them. The larger the bottle, the
more likely it is that the remaining crystals will be hydrated
every time the bottle is opened. The longer it takes to weigh the
crystals, the more hydrated they will become.
Peel solutions are therefore prepared by diluting crystals
that are gradually becoming more and more hydrated: at the
same weight, the pharmacist is in fact weighing TCA crystals
that are slowly swelling with water. The solutions that he pre-
pares are more and more diluted and therefore less and less
effective. The doctor, for his part, gets into the habit of apply-
ing increasingly weaker TCA peels with increasing firmness, in
spite of the fact that the same labels show the same concentra-
tion. The doctor therefore gets used to applying ever increas-
ing volumes of peel solution to achieve the same results—until
the day when the pharmacist starts using a new bottle of pure
TCA crystals and makes up a peel solution with fresh, anhy-
drous crystals that are more aggressive than the “old” hydrated
crystals. Applying this new and more concentrated solution of
course results in a peel that is deeper than the doctor expected,
and the risk of complications is increased, even though there is
no apparent difference in the application procedure.
Unlike pure crystals, TCA solutions do not hydrate by
themselves. It is therefore safer not to keep TCA in crystal form
and instead to use reconstituted solutions whose concentration
is more stable than crystals.
Inhomogeneity of TCA Solutions
A solution is said to be homogeneous when the different elements
of which it is made are evenly distributed in the container that
holds it. The homogeneity of peel solutions is one of the essen-
tial elements of their safety.
Simple Aqueous Solutions of TCA
Unfortunately, TCA simple aqueous solutions (TCA–SAS)16 are
neither homogeneous nor stable. The TCA molecule is very
mobile in the solution, and its motion has both a random ele-
ment and a component determined by its chemical structure.
When an aqueous solution of TCA is left in an unmov-
ing container, the concentration of the solution does not remain
uniform. The TCA temporarily becomes more concentrated
in some parts of the container and more dilute in others. For
example, if a TCA solution of 33% m/m is prepared and left at
room temperature, some regions of the solution will have a con-
centration of 35% for a certain length of time while neighboring
regions will have concentrations of 30% or 40% (Figure 12.6).
As this process continues, the region that just had a concentra-
tion of 35% will now have a concentration of 37%, while other
areas of the solution will have different concentrations again,
for example 25% and 29%, and so on.17
Depending on the position of the tip of the needle used for
taking the acid out of the bottle, the solution will be more con-
centrated or more dilute. A solution that is too dilute or too con-
centrated could be applied to different parts of the face. Simple
aqueous solutions of TCA have to be mixed continuously, both
when they are being taken out of the bottle and while they are
being used. Certain complications that arise unexpectedly after
a TCA–SAS peel can be explained—at least partially—by this
phenomenon of inhomogeneity.
Cl
C
C
Cl
Cl
O
OH
Figure 12.5  Chemical structure of trichloroacetic acid.

Trichloroacetic acid: GENERAL INFORMATION, TOXICITY, FORMULATIONS, AND HISTOLOGY      77
Awareness of this problem led to the rapid development
of new TCA peel formulas between 1990 and 2000. One of the
first solutions developed was the New Peel combination of
TCA and Mikuda complex. The Soft Peel formulation used asi-
aticosides and ginsenoids, glycerol, urea (carbamide), sorbitan
monolaurate, and methyldibromo-glutaronitrile, among other
ingredients. Easy TCA, Unideep, and Only Touch peel (OTP)
provided another answer to the problem: these stabilized solu-
tions consist of a base solution to which a determined quantity
of 50% m/m TCA is added. There are no complicated calcu-
lations to be performed; the directions for use state precisely
what volume of 50% m/m TCA solution should be added to
the base solution to make up the Easy TCA, Unideep and OTP
solutions, which provide peels to the basal layer, the papillary
dermis, and the reticular dermis, respectively.
Calculating the Concentration of TCA
Since TCA peels first came into use, practitioners have suffered
from a lack of standardization regarding how a solution’s con-
centration is to be calculated. The calculation can be done in dif-
ferent ways: by mass per mass (m/m), mass per volume (m/v),
or mass plus volume (m + v, e.g., m + 100 ml). There are also dif-
ferent formulas for diluting these solutions using approximate
curves. Therefore, “50%” TCA has little meaning if we do not
know whether the calculation is m/m, m/v, or m + 100 ml. In
1995 and 1996, Trauchessec and Pissot18,19 suggested standard-
izing the calculation of the concentration of a TCA solution by
expressing it in m/m, which is the only logical way of calculat-
ing a percentage. It should be possible to make a strict compari-
son of the terms of a percentage. For example, the carbohydrate
content of a meal is given as a percentage: a content of 20% car-
bohydrate means that 100 g contains 20 g of carbohydrate and
80 g of something else. Unless it is clearly indicated on the pack-
aging, there is no way of knowing that a volume of 100 ml of this
meal would contain 20 g of carbohydrate. It would be impossible
to understand exactly how much carbohydrate is in the food.
Unfortunately, this type of calculation (weight by volume, w/v)
is widely used in some countries: a volume of 100 ml of TCA
solution contains x grams of TCA. If we know the concentra-
tion in w + v only, it is difficult to calculate the exact amount of
TCA in the solution. To get the correct answer, one has to calcu-
late mass with mass, and volume with volume, and not volume
with mass.20 Examples of calculations of concentration using the
w/w, m/v, and w + v methods are given in Boxes 12.1–12.3.
Methods of calculation based on volume lead to values
of concentrations that can be as high as 140%. Because a “0%
solution” is pure water and a “100% solution” pure TCA, values
greater than 100% are essentially meaningless. Ideally, there-
fore, these methods should not be employed for the calculation
of concentrations—only the m/m method should be used.
Nevertheless, for the sake of simplicity, pharmacists often
prefer to use dilutions in volume whenever possible, as they
can buy “standardized” TCA solutions at 20%, 50%, and so on.
Then, in theory, all the pharmacist has to do is add 100 ml of
water to 100 ml of TCA solution at “50%” to get a “25%” solu-
tion. It is not easy for a doctor to calculate how much TCA these
solutions contain. Examples of calculations of dilutions using
the m/m, m/v, and m + v methods are given in Boxes 12.4–12.6
and Tables 12.1 and 12.2.
Publications Can Be Misleading
A major problem arises when reading publications from dif-
ferent sources. Suppose that an American doctor wants to
use a peeling technique described by a European author who
gives concentrations in m/m but does not mention this in the
publication, as is too often the case. The American doctor gets
his pharmacist to make up the solution as described by the
European doctor. The American pharmacist, however, prepares
a solution in m/v or m+v, or even dilutes it as described in the
BOX 12.1  TCA Solution at 50% Mass per Mass (m/m)1
100 g of TCA solution at 50% m/m contains 50 g of pure,
unhydrated TCA crystals and 50  g of water. 100  g of this
solution is not, however, 100 ml, but only 79 ml. In fact, 1 g
of TCA displaces 0.6 ml and not 1 ml of water.2 Scientifically,
this is the most rigorous method of calculation, as 100 ml of
a solution at 50% m/m would contain (50/79) × 100 = 63.3 g
of TCA.
%
Mass of
TCA (g)
Volume of
water (ml)
Final
mass (g)
Final
volume (ml)
10
10
90
100
96
20
20
80
100
92
30
30
70
100
88
40
40
60
100
83
50
50
50
100
79
60
60
40
100
75
70
70
30
100
71
1. Taken from Trauchessec JM, Pissot F. Solutions d’acide tri-
chloroacétique masse pour masse pour peelings derma-
tologiques. Les Nouvelles Dermatologiques. 1996; 15:
252–55, with the authors’ permission.
2. According to Trauchessec, the exact value is 0.59 ± 0.01. The
value of the constant 0.60 used here is an acceptable
approximation. It means that 1 g of TCA displaces 0.6 ml of
pure water, whatever the concentration of the solution.
29%
40%
25%
37%
30%
15%
(a)
(b)
Figure 12.6  Inhomogeneity of simple aqueous solutions of TCA.
(a) A solution with a presumed concentration of 33% contains
mobile regions of different concentrations. (b) At a later time, the
same TCA solution with a presumed concentration of 33% con-
tains mobile areas of concentrations that are different.

78      Textbook of Chemical Peels
previous section. The European technique may well be based
on an aggressive TCA, with a concentration of 45% m/m. The
American doctor orders a solution at 45% from his pharmacy
but is in fact using a concentration of 38.1% m/m when the cal-
culation has been made at 45% in m + 100 ml. A solution with
a concentration of 31% m/m will clearly not produce the same
results as a concentration of 45% m/m. The American doctor
cannot achieve the same results as the European author, whose
results might therefore easily be considered exaggerated or
even rigged.
The situation is more serious when a European doctor
wants to use an American application technique with a TCA
solution at 50% m + 100 ml. This solution contains 50 g of pure
TCA to which 100 g of water is added. The final volume of the
solution will be 129 ml for a mass of 150 g, and 100 g of this
BOX 12.2  TCA Solution at 50% Mass per Volume (m/v)1
This solution is prepared in the following manner: 50 g of TCA
is diluted in a small amount of distilled water to get a small
amount of solution, then the volume is made up by adding
distilled water until the final volume reaches 100 ml. To get
100 ml of solution and an end mass of 121 g, 50 g of TCA will
be dissolved in 71 ml of water. This method of calculation is
easy for the pharmacist, as 100 ml of solution contains 50 g
of TCA (100 g of this solution would contain 41.32 g of TCA).
%
Mass of
TCA (g)
Volume of
water (ml)
Final
mass (g)
Final
volume (ml)
10
10
94
104
100
20
20
88
108
100
30
30
82
112
100
40
40
77
117
100
50
50
71
121
100
60
60
65
125
100
70
70
59
129
100
1. Taken from Trauchessec JM, Pissot F. Solutions d’acide
trichloroacétique masse pour masee pour peelings derma-
tologiques. Les Nouvelles Dermatologiques. 1996; 15:
252–55, with the authors’ permission.
BOX 12.3  100 ml1
This method of preparation involves adding 100 ml of water
to 50 g of pure TCA crystals. The final volume of this solution
is 129 ml for a mass of 150 g. 100 ml of this solution contains
38.75 g of TCA, while 100 g of this solution m + 100 ml con-
tains 33.33 g of TCA. This is the easiest but also the worst
method of calculation, as it is extremely difficult to work out
the exact amount of TCA.
%
Mass of
TCA (g)
Volume of
water (ml)
Final
mass (g)
Final
volume (ml)
10
10
100
110
106
20
20
100
120
112
30
30
100
130
117
40
40
100
140
123
50
50
100
150
129
60
60
100
160
135
70
70
100
170
141
1. Taken from Trauchessec JM, Pissot F. Solutions d’acide tri-
chloroacétique masse pour masse pour peelings derma-
tologiques. Les Nouvelles Dermatologiques. 1996; 15:
252–55, with the authors’ permission.
BOX 12.4  Dilution of a Base Solution
at 50% Mass per Mass (m/m)
100 g of a solution of TCA at 50% m/m contains 50 g of TCA
and 50 g of water (50 g of water is in fact equivalent to 50 ml
of water) and has a volume of 79 ml. If 79 ml of solution con-
tains 50 g of TCA, then 1 ml contains 0.633 g of TCA, there-
fore 100 ml of TCA solution at 50% m/m contains 63.3 g of
TCA. If this solution is diluted with the same volume of water
(i.e., 100 ml), it produces 200 ml (but not 200 g) of TCA solu-
tion, in which there is still 63.3 g of TCA. Therefore, 100 ml of
the new diluted solution contains 31.65 g of pure TCA.
BOX 12.5  Dilution of a Base Solution
at 50% Mass per Volume (m/v)
100 ml of TCA solution at 50% m/v contains 50 g of TCA
diluted in 71 ml of water, to give a solution with a volume of
100 ml for a mass of 121 g. If 100 ml of pure water is added to
100 ml of solution at 50% m/v, it produces 200 ml of solution,
which weighs 221 g and contains 50 g of TCA. 100 g of this
solution contains 22.6 g of TCA, while 100 ml of the same
solution contains 25 g.
BOX 12.6  Dilution of a Base Solution at
50% Mass + Volume (m + 100 ml)
100 ml of TCA solution at 50% m + 100 ml contains 38.75 g of
pure TCA for a mass of 116.27 g. Adding 100 ml of water with
the aim of converting the theoretical concentration into 25%
therefore gives a solution of volume 200 ml, whose mass is
226.27 g and which still contains the same 38.75 g of TCA.
100 g of the new solution therefore contains 17.12 g of TCA.
100 ml of the new solution contains half of the 38.75 g, which
is 19.38 g of TCA.
Table 12.1  Calculation of a TCA Solution at 50% in Mass or in
Volume
Method of calculation
m/m
m/v
m + 100 ml
Grams of TCA in 100 ml
63.3
50
38.75
Grams of TCA in 100 g
50
41.32
33.33
Table 12.2  Obtaining a Solution at “25%” by Adding 100 ml of
Water to a Solution at “50%”
Method of calculation
m/m
m/v
m + 100 ml
Grams of TCA in 100 ml
31.65
25
19.38
Grams of TCA in 100 g
25
22.6
17.12

Trichloroacetic acid: GENERAL INFORMATION, TOXICITY, FORMULATIONS, AND HISTOLOGY      79
solution is actually equivalent to 33% m/m. The American
author who applies a TCA solution at 50% m/v—which is in
fact a European 33% m/m solution—to a patient’s face can
achieve excellent results. The European doctor, who wants to
achieve the same results by applying a solution at 50% m/m
provided by the pharmacist, is running a huge risk of burn-
ing the patient’s skin and causing hypo- or hyperpigmentation,
scarring,21 and other problems. It is therefore essential to stipu-
late the type of concentration to use, and this is one of the first
pitfalls awaiting any doctor who is new to peeling.
The technique for applying TCA, which is actually very
easy, has for a long time been made difficult because of the differ-
ent methods for calculating concentrations (see earlier discussion)
and the approximate explanations given in many publications.22
There are many inconsistencies: some publications consider a
TCA peel at 50% to be a “superficial peel.” Yet we know that a
peel at 50% reaches the reticular dermis easily and quickly, and
can sometimes even go beyond it: this is a deep peel—in most
cases too deep. This solution penetrates the whole of the papil-
lary dermis immediately, achieving a “medium” or “deep” peel,
but certainly not a superficial one. The same solution at 50%, but
calculated in m + 100 ml, would be equivalent to a 33.3% m/m
solution, and the first coat of TCA at 33% m/m would soon reach
the papillary dermis. It is then difficult to understand how any-
one can say that a “TCA peel at 50% produces a superficial peel”:
in whatever way the calculation is made, it is wrong and a TCA
solution at 50% will produce, at the very least, a medium-depth
peel even if it is calibrated in m + 100 ml. The type of applicator
used, the number of coats, and the total quantity of TCA applied
to the skin, as well as any prepeel preparation and other consid-
erations, must also be taken into account.
Histological studies have compared the depths reached
by different concentrations of TCA used in conjunction with
different techniques such as dry ice or prior application of
Jessner’s solution. A histological study by Brody and Stegman,
at 3, 30, and 90 days,23 showed that the deeper the injury, the
more necrosis and regeneration are histologically visible. It has
thus been shown that three successive applications of TCA cause
deeper necrosis than one application.24 The technique used in
this study involved the application of TCA at a concentration of
35%—presumably calculated in mass per volume, although it
was not stated whether this was a w/v calculation, m + 100 ml
calculation, or a dilution of TCA solution. The Jessner’s solution
in the study was supposed to be prepared from lactic acid crys-
tals rather than from an 80% (w/w, w/v?) lactic acid solution.
This solution was applied with a cotton bud: the volume, form,
and texture of the cotton bud have an influence on the quan-
tity of solution that comes into contact with the skin. The dry
ice was applied firmly (how firmly was not stated) in acetone
(exactly how much and at exactly what temperature were also
not stated) for 15 seconds. The importance of studies such as
this should not be underestimated, but it is necessary to draw
attention to the number and importance of the variables that
have to be taken into account when evaluating results.
A Good Method of Calculation
A consistent method of calculating concentrations must be
adopted. It would of course be preferable to use pharmacologi-
cal concepts such as molar mass, but practitioners are not used
to handling such data. From a practical point of view, there
are two units of measurement that are easily accessible: mass
and volume. As we have just seen, the only acceptable values
are calculations in m/m (if we are referring to mass) or in m/v
(if we are referring to volume). Measurements in m + 100 ml
are too approximate, as is using dilutions of preexisting solu-
tions. Anyone is capable of measuring an approximate volume,
although not an exact one, and this introduces another mar-
gin of error. With the help of precision scales, it is possible to
measure a mass precisely—more precisely, in any case, than
by judging gradients on a measuring glass with the naked eye.
This confusion over concentrations is extremely dangerous,
and a standardized concentration should be used to avoid dis-
appointment as well as complications. McCullough25 has drawn
attention to the discrepancies between calculations of TCA con-
centrations but prefers to use the m/v method. We have chosen
to calculate the concentration in m/m for the following reasons,
as expressed by Trauchessec:19
1.
Measuring mass is more precise than measuring volume.
2.
A real percentage can only be calculated using m/m or v/v.
3.
The use of approximate dilution curves is avoided with
m/m calculations.
4.
With m/m calculations, there is no potential for errors
caused by the existence of three types of mass per volume
concentrations: m/v in QS, adding 100  ml of water to a
mass of TCA, or diluting preexisting TCA solutions.
5.
The m/m calculation does not produce values of TCA “con-
centrations” reaching 140%—which make no sense.
6.
Finally, the size of TCA crystals, the compactness of the
mass of crystals, and the temperature of the solution are
elements that have to be taken into account when making
m/v or m + v calculations. The m/m calculation does not
depend on these parameters.
Easy TCA, Unideep, and Only Touch Solutions
Easy TCA is a stabilized,26 homogeneous and adjuvanted solu-
tion with a final TCA concentration of 15% m/m, combined
with alpha hydroxy acids (AHAs), antioxidants, vitamins, and
saponins. Unideep is a TCA peel based on the same principles
as Easy TCA and reaches the papillary dermis readily and
evenly; it has a TCA concentration of 23% m/m. The application
protocols for these two peels allow all depths to be reached.
There is no point using higher concentrations that could cause
complications (see Chapter 37).
TCA IN SIMPLE AQUEOUS SOLUTION
Simply diluting TCA crystals in water produces an unstable
solution whose characteristics have been discussed earlier in
this chapter. TCA-SAS solutions are the cheapest a doctor can
buy. They are also the most dangerous.27,28 It is clear from the
literature on chemical peels how dangerous these solutions
are; most photographs of serious complications show patients
treated with TCA–SAS. It is clear that an experienced doctor can
avoid most of the serious complications, but an inexperienced
one can easily fall into every trap that these cheap solutions
set. To paraphrase: While it is cheaper to spend the night on a
park bench in a big city than to rent a room in a decent hotel, it
is nonetheless true that you would get a much better and safer
night’s sleep in a hotel room than you would in the park. Even
though some of the world’s best peelers can use TCA–SAS with
complete safety, it is still true that the vast majority of complica-
tions occur after the application of these cheap solutions. Some
ill-informed doctors have ended up claiming that TCA simply
cannot be used to treat melasma, for example.

80      Textbook of Chemical Peels
Reading the textbooks on chemical peels is very instruc-
tive, and the pictures of complications often reflect the com-
plexity of using TCA–SAS correctly. Today’s new TCA peel
solutions have been developed with a view to convenience
and safety. The author can already hear reproaches from those
who claim the contrary and are perfectly able to use TCA–SAS
safely, but he can also hear the sobs and regrets of practitioners
who listened to them and whose patients have suffered for it.
The simple aqueous solution of TCA was born in the 19th cen-
tury. It had its day; now practitioners should move on.
“ADJUVANTED” TCA
Applying TCA–SAS to the skin causes frosting that is rarely
even,28 especially when using intermediate concentrations.
Applying TCA–SAS at 10% m/m does not usually cause any
frosting and is almost risk-free; applying TCA–SAS at 50%
m/m causes very rapid frosting whose depth is difficult to
evaluate and control.29 Intermediate aqueous concentrations
(e.g., at 25% or 30% m/m) do not penetrate evenly and produce
intraepidermal peel zones next to peel zones to the papillary
or reticular dermis. It is difficult to get even frosting, and the
results of the peel are not homogeneous: undertreated areas are
next to overtreated areas that could easily create problems with
postinflammatory hyperpigmentation (PIH), hypopigmenta-
tion, or even scarring (Figure 12.7).
Various adjuvants have been added to TCA to even out its
effect. The term adjuvanted is used to describe a TCA solution
to which something has been added to enhance or even out its
action. Many different products have been added to TCA.
Glycerol
Glycerol (Figure  12.8), also known as glycerine, glycerin,
1,2,3-propanetriol, or 1,2,3-trihydroxypropane, has a molecular
weight of 92.09. It is often used as an antimicrobial preservative
(in concentrations >20%), a humectant (≤ 30%), an emollient (≤
30%), or a solvent. It is used in cosmetic products as well as in
parenteral or oral preparations. Adding glycerol to a solution
increases its viscosity. Glycerol, being an alcohol, potentially
induces formation of esters components in the solution; esters
have no peeling potential. Glycerol does not oxidize easily on
contact with air. It is not toxic: after absorption by the diges-
tive tract, it is metabolized into carbon dioxide and glycogen or
is used for lipid synthesis. High doses of glycerol taken orally
have a laxative effect and can cause headaches, hyperglyce-
mia, thirst, and nausea. Glycerol is also used in the laboratory
as a protein stabilizer (which seems paradoxical, considering
that the effect sought by applying TCA is the destruction of
proteins).
Soft Peel was presented as a solution for improving the
tolerance and effectiveness of TCA. Nevertheless, adding glyc-
erol did not eliminate the need to prepare the skin beforehand,
3 weeks before the peel:30
•
With a depigmenting formula to prevent pigmentary
changes in patients with a high skin phototype (over
Fitzpatrick IV); it was also necessary to wear a total sun-
block before this peel, which suggests that pigmentary
changes are common after this type of peel.
•
With retinoids or benzoyl peroxide in cases of acne: treat-
ment with isotretinoin was not given as a strict contrain-
dication to Soft Peel on condition that the daily prescribed
dose 2 or 3 weeks earlier did not exceed 0.3 mg/kg per day.
•
With tretinoin at 0.05% once a day in the evening combined
or not with glycolic acid to increase and even out penetra-
tion of the TCA and accelerate regeneration of the epider-
mis after the peel, which suggests that the solution did not
penetrate evenly and readily and that healing was slow.
The total number of “soft peels” required was 5–10, with
an interval of 8–21 days in between, depending on the depth
reached by each peel. The peel solution had to be “neutral-
ized” with water as soon as frosting occurred.31 It should be
Figure 12.7  Technical error during the treatment of stretch marks
using an abrasive procedure (see Chapter 21). Typically, a halo of
hyperpigmentation surrounds the depigmented area, which in turn
surrounds a scar response. Hyperpigmentation develops where
the peel solution goes slightly deeper than it should, and scars
form where the peel is much too deep.
H
C
C
C
H
H
H
H
OH
OH
OH
Figure 12.8  Chemical structure of glycerol.

Trichloroacetic acid: GENERAL INFORMATION, TOXICITY, FORMULATIONS, AND HISTOLOGY      81
remembered, however, that adding water to an acid solution
does not neutralize it but simply dilutes it.
The pH increases very slowly when the solution is
diluted, and large quantities of water are needed (Figure 12.9).
Rinsing with water was necessary, however, to remove the
excess solution that was no longer needed after the appear-
ance of frosting on the skin. It would be more accurate to say
remove any surplus solution with water as soon as frosting
appears instead of neutralize the acid. Without rinsing, the
TCA in the TCA–glycerol solution would continue to destroy
the skin proteins and deepen the effect of the peel. Choosing
the right moment to rinse is therefore essential and has to be
timed very carefully, which is not easy for an inexperienced
doctor. Some formulations (called “composite” or “composi-
tum”) still use solutions with glycerol and the postpeel rinsing
technique, which is both restrictive and the source of errors.
It is also important to make sure that the water does not carry
the TCA into the eyes or onto the neck and décolletage, where
it will cause an accidental peel.
Glyceryl Monooleate
Some glycerol derivatives can be used as adjuvants. Glyceryl
monooleate (Figure 12.10), for example, is a nonionic surfactant
and polar lipid with a molecular weight of 356.55. It is a mono-
ester of glycerol in which one of the hydroxy groups is replaced
by a long side-chain derived from oleic acid (CH3(CH2)7CH =
CH(CH2)7COOH).32
Propylene Glycol
Propylene glycol (Figure 12.11), also known as 1,2-propanediol
and 1,2-dihydroxypropane, has a molecular weight of 76.1. It
is used as an antimicrobial preservative (at 15%–30%), a dis-
infectant, a humectant (at 15%), a solvent or co-solvent, and
a stabilizer for vitamins, both in cosmetics and in parenteral
pharmaceuticals (10%–60%). Although propylene glycol is
considered to be nontoxic, parenteral administration of high
doses can cause problems, especially in patients with renal
insufficiency. Propylene glycol, being an alcohol, potentially
induces formation of esters components in the solution; esters
have no peeling potential. Its disinfecting power is slightly
lower than that of ethanol. Propylene glycol is stable at low
temperatures. At high temperatures, it tends to oxidize and
form lactic acid, acetic acid, pyruvic acid, and propionalde-
hyde. Locally, propylene glycol is more of an irritant than
glycerol, especially if it comes into contact with the mucous
membranes or is used under occlusion. It is neither mutagenic
nor teratogenic.
Stability of TCA Solutions with
Glycerol or Propylene Glycol
Attempts to stabilize TCA solutions by adding glycerol (“soft
peeling”31) or propylene glycol improved the safety of TCA
peels, although it did not necessarily make them completely
stable. Moreover, the addition of glycerol or its derivatives was
still empirical and varied from one doctor to another—more of
a do-it-yourself approach than a professional one. It is difficult
to compare the different solutions because the exact concentra-
tions of these adjuvants were neither uniform nor even known
for certain. Soft Peel involved the ad hoc combination of TCA
at variable concentrations with the same quantity (volume) of
glycerol.
Other Adjuvants
Other attempts to stabilize and even out TCA were made in the
1990s.
“Enzymatic” TCA
An enzyme is, by definition, a protein. TCA coagulates pro-
teins. It is therefore difficult to include active proteins and TCA
in the same solution, because even if some enzymes are acid
resistant (e.g., in the stomach), the conditions for acid resistance
are strict and not reproducible in a TCA solution. To the author’s
knowledge, there is no preparative approach that would allow
proteins to be encapsulated in nanosomes, liposomes, cyclo-
dextrins, and so on, to protect them from the coagulating action
of concentrated TCA.
H
C
C
C
H
H
H
H
O
C
C17H33
OH
OH
O
Figure 12.10  Chemical structure of glyceryl monooleate.
H
C
C
C
H
H
H
H
H
OH
OH
Figure 12.11  Chemical structure of propylene glycol.
Figure 12.9  Effect of dilution on the pH of 5 ml of an organic acid
solution at pH 2.7: 80 ml of water must be added before the pH
rises a little more than 1 point.

82      Textbook of Chemical Peels
Sorbitan Monolaurate
Sorbitan monoesters are partial esters of sorbitol with fatty
acids (monolaurate in this case). They have a molecular weight
of between 346 and 964. Sorbitan monolaurate is widely used in
cosmetics, the food industry, and pharmaceutical preparations.
Sorbitan monoesters are non-ionic surfactants, and dissolving
and dispersing agents. One of the problems of using sorbitan
monoesters is that in the presence of strong acids (like TCA)
they tend to form soaps that have no power to attack the skin.
This is partly why TCA “adjuvanted” with sorbitan monolau-
rate is less aggressive for the skin.
Phenoxyethanol
Phenoxyethanol, C6H5OCH2CH2OH, also known as ethylene
glycol monophenyl ether, 2-hydroxyethyl phenyl ether, 1-hydroxy-
2-phenoxyethane, 2-phenoxy-ethyl alcohol, and 2-phenoxyetha-
nol, has a molecular weight of 138.16. Phenoxyethanol, being an
alcohol, potentially induces formation of esters components in the
solution; esters have no peeling potential. It is a simple disinfec-
tant in the adjuvant solution, an antimicrobial agent that seems
not to have a real adjuvant effect on the peel.
Chelation of TCA
Some TCA masks33 have been presented as “chelated” TCA.
Chelation34 is a medical therapy that aims to detoxify the body
of harmful minerals and metals. Chemically, chelation is the
process by which an organic substance (the chelator) binds
metal ions (iron, copper, lead, calcium, etc.) into inactive, non-
toxic, and water-soluble complexes that are easily eliminated in
the urine. Intravenous chelation therapy (e.g., with ethylenedi-
amine tetra acetic acid, EDTA) is often used to treat poisoning
with heavy metals, including lead. The use of the term chelation
therefore seems inappropriate as far as TCA is concerned, and
has no chemical basis because TCA is not a metal. The little
information available states that chelation reduces the speed of
penetration of TCA and therefore its depth of action.35 Might
what we call chelation be partial inactivation of the TCA? The
directions of use for Accu Peel state that a “process called che-
lation allows the TCA to reach an even depth at the same time
as using lower concentrations of TCA.” Might chelation, on the
contrary, be a process that activates the TCA? But how can TCA
be activated?
The directions for use of TCA Cream Peel tell us that,
thanks to chelation, not only is this peel as deep and smooth
(sic) as regular TCA but also that it uses much milder concen-
trations (the stakes are being raised) so there is less pain and
stinging and healing is faster. Is chelation the ultimate answer
for TCA? The Holy Grail of the peeler?
The Plastic Surgery Group states that “chelation” of Accu
Peel, on the contrary, provides a superficial peel that heals more
quickly—which at least seems logical. Chelation is therefore
presented as the ultimate solution to all the problems posed
by TCA. The most scientific-sounding explanation seems to be
of a specific technique where the TCA binds to metallic ions
in bentonite clay. It is not therefore strictly chelation, which
would imply the binding of metallic poisons and their elimina-
tion through urine. But it is partly true insofar as an organic
substance (the TCA) binds with silicon and metal ions (alumi-
num and magnesium). Even if the process is the opposite of
chelation—because in this case it is the TCA itself that is the
chelating agent—this explanation merits closer examination to
understand the possible interactions between the TCA and the
structure of the clay.
TCA in Clay Masks
TCA sometimes comes in the form of a clay paste. Generally,
clays consist of two types of compounds: aluminum silicates
(bentonites) and magnesium silicates (hectorites). Clays36 are
made up of stacked three-layer platelets (Figure 12.12): a middle
layer of magnesium oxide (in the case of hectorites) or alumi-
num oxide (in the case of bentonites) surrounded by two layers
of silicon dioxide (silica). The lateral surfaces of each platelet are
positively charged,37 and the lower and upper surfaces are neg-
atively charged.38 The clay platelet therefore reacts like a dipole,
and the different particles rearrange themselves depending on
the electrical charges that encourage contact between the lat-
eral surface and the upper surface. Clay has a “house of cards”
structure, and macroscopically forms a coarse gel with a grainy
texture in the aqueous phase.
The TCA molecule is itself electrically neutral. When it is
in an unbuffered solution, it more or less completely breaks up,
releasing its proton (H+) into the solution, which then becomes
acidic. The TCA, without its proton (i.e., trichloroacetate anion),
has an overall negative charge that can therefore combine elec-
trically with the positively charged lateral surfaces of the clay,
while the positively charged protons will combine more read-
ily with the lower and upper surfaces of the negatively charged
clay particles (Figure 12.13). The protons therefore combine with
the oxygen atoms of the silica molecules on the lower and upper
surfaces, whereas the negatively charged trichloro-acetate anion
will combine with the metallic cations on the other surfaces of
the clay particles. This then explains how the TCA binds with
metallic ions. It is easy to understand how this might stabilize
the TCA, as once it has broken up, it binds electrically with the
different parts of the clay particles. It is, however, difficult to
understand the real clinical advantage of this combination, as the
protons that produce the peeling effect are still attached to the
part of the TCA that has not broken up or else they have to break
away from the clay to be effective. It could then be argued that
the protons (and the trichloroacetate) and the clay are relatively
united and that the TCA in a clay mask will act more slowly and
be less aggressive. It is difficult to reconcile this with the state-
ment that a low-concentration TCA clay mask produces the same
effect as a more concentrated water-based TCA in which all the
molecules exert their peeling effect at the same time.
It cannot seriously be claimed that a clay paste of “che-
lated” TCA at 20% is equivalent to any other TCA liquid at
45%–50%. Even then, it would be necessary to know whether
the concentration is m/m, m/v, or m + v. It cannot possibly be
m/m, as a TCA at 50% m/m is extremely aggressive and causes
Silicon dioxide
Aluminum or magnesium oxide
Silicon dioxide
++++
++++
++++
++++
++++
+
+
+
+
+
+
++++
– – – – – – – – – –
– – – – – – – – – –
Figure 12.12  Clays consist of a stack of platelets that are elec-
trically linked. This diagram shows the typical structure of a clay
platelet and its electrical charge.

Trichloroacetic acid: GENERAL INFORMATION, TOXICITY, FORMULATIONS, AND HISTOLOGY      83
more complications than effective results. Besides, 20% TCA
masks are marketed as superficial peels, which is incompatible
with the gratuitous claim that “20% in mask form is equiva-
lent to 50% in liquid form” but completely compatible with
the scientific explanation given earlier. Another major prob-
lem comes from the fact that the clay mask forms a coarse and
opaque layer: it is impossible to observe the effect of the TCA
directly and continuously through the clay mask (Figure 12.14).
One common method of monitoring the peel consists of using a
tongue depressor to remove the clay from a small area to see if,
or how much, frosting has occurred. If there is no frosting, the
acidified clay is replaced. This examination is repeated after a
few minutes or if the patient makes any comment. It should be
noted that removing the clay with a spatula creates an abrasion
on the skin where the acid can penetrate more deeply. The next
time, therefore, the same area must be checked again as well as
a different area.
When a TCA paste is called “homogeneous,” it should
not automatically be assumed that the TCA is distributed
evenly, although it may well be. One should assume that the
paste itself has a homogeneous consistency and is not grainy. It
is possible—though not easy—to spread TCA homogeneously
in a clay paste. However, the even distribution of TCA in a paste
does not in itself guarantee that the acid will penetrate the skin
evenly.
Another argument that counters the claim that lower
concentrations are more effective is that the application tech-
nique for a TCA mask involves degreasing the skin and apply-
ing glycolic acid or tretinoin beforehand.35 This makes the skin
far more permeable and enhances the penetration of the TCA,39
which means being very careful about how long the paste
remains in contact with the skin.
Some TCA clay pastes are presented as causing simple
erythema with no protein coagulation, but they nevertheless
have a downtime of 6–8 days.35
The absence of frosting is compatible with a superfi-
cial peel but not with an improvement in the appearance of
Silicon dioxide
Aluminum or magnesium oxide
Silicon dioxide
++++
++++
++++
++++
++++
++++
–
–
–
– – – – – – –
– – – – –
–
–
Silicon dioxide
Aluminum or magnesium oxide
Silicon dioxide
++++
++++
++++
++++
++++
++++
+
+
+
+
+
+
–
–
–
– – – – – – –
– – – – –
–
– – – – –
Silicon dioxide
Aluminum or magnesium oxide
Silicon dioxide
++++
++++
++++
++++
++++
++++
–
–
–
– – – – – – –
– – – – –
–
– – –
Silicon dioxide
Aluminum or magnesium oxide
Silicon dioxide
++++
++++
++++
++++
+
+
+
+
+
+
++++
++++
–
–
–
– – – – – – –
– – – – –
–
– – – – –
–
Silicon dioxide
Aluminum or magnesium oxide
Silicon dioxide
++++
++++
++++
++++
+
+
+
+
+
+
++++
++++
–
–
–
– – – – – – –
– – – – –
–
– –
H+
H+
H+
H+
O
O
C
CL3
O
O
C
CL3
H+
O
O
C
CL3
H+
H+
O
O
C
CL3
O
O
C
CL3
H+
H+
H+
+
+
+
+
O
O
C
CL3
Figure 12.13  A possible arrangement of TCA in a solution with clay in the gel phase, on the basis of electrical charges.
Figure 12.14  TCA green clay mask (TCArcil mask). The hands
and forearms are covered in a clay paste layer that spreads easily.

84      Textbook of Chemical Peels
deep wrinkles, which can only be treated with a deep peel.
Then again, a downtime of 6–8 days is not compatible with a
superficial peel, as it is the same as the downtime following a
“medium” TCA peel to the papillary dermis.
The TCA mask is not the easiest40 or safest of peels, as it is
not possible to check in real time whether the TCA is penetrat-
ing too deeply under the mask. It does, however, make applica-
tion a little easier for doctors who doubt their ability to apply
a superficial TCA peel evenly. We can therefore conclude by
saying that TCA masks are easy to apply but difficult to moni-
tor. Even if “chelation” makes the clay mask less aggressive, it
is on the whole not as safe as an “open” TCA peel, which can
be monitored at all times. The author’s experience with a TCA
mask preceded by a glycolic acid mask is in the context of a
regular medium-depth TCA peel to the papillary dermis.
HISTOLOGY
Even though histological sections taken 30 minutes after the
application of a medium-depth TCA peel on the skin have not
revealed any skin necrosis, and even though histologically
everything appears normal, it is certain that necrosis is taking
place both clinically and chemically. The epidermis is func-
tionally dead, although it appears to be histologically normal.
Maybe this can be explained by the protein-coagulating action
of the TCA: with conventional histology, it is not possible to
see membrane proteins (essential to cell life) coagulating. It is
only later on that necrosis can be detected histologically when
the normal cell structure has radically changed as a result of
its protein membranes becoming devitalized. The overall his-
tological effect of a TCA peel consists of the destruction of the
living cells of the epidermis and possibly the dermis (the depth
of destruction depends on the concentration used). Abnormal
keratinocytes are replaced by healthy cells from deep surviv-
ing islets of keratinocytes, the pilosebaceous units, and the
sweat glands.41 As the skin reepithelializes, new collagen is
formed.
The depth of skin necrosis is directly proportional to the
concentration of the TCA. Necrosis should not be the only end-
point of a TCA peel—stimulation also plays an important role.
Repeated application of less concentrated TCA helps rebuild
the papillary dermis directly and/or indirectly as a result of the
repeated dermal irritation of the peel-induced inflammation. It
is possible to reach the dermis using a low-concentration solu-
tion applied to an epidermis that has been made temporarily
more permeable by a prior peel or “robust” preparation.
TCA peels allow different depths of penetration to be
reached (Table 12.3).
A study by Roenigk41 shows that regeneration of dermal
collagen starts within 2–3 weeks. The increase in papillary der-
mal collagen and the production of elastic fibers continues for
6 months. Another study42 on mice artificially photoaged by
exposure to UV rays compared the histological effects of four
different types of peels against a control group:
•
50% glycolic acid.
•
30% TCA (m/v or m + v not specified).
•
50% TCA (m/v or m + v not specified).
•
Phenol peel (Baker Gordon’s formula).
In all of the peel groups, the concentration of collagen
increased from the 3rd day, fell around the 7th day, and reached
a positive peak around the 28th day. There was more of an
increase with the TCA and phenol peels than with the glycolic
acid. There was a significant increase in the concentration of
glycosaminoglycans with the 50% TCA and phenol at 14 and 28
days. On the 60th day, the dermal concentrations both of col-
lagen and glycosaminoglycans had returned to their original
values in all of the groups.
These findings cannot be considered as proof that these
peels are not clinically effective, as the structure of the epider-
mis and dermis improved histologically, the collagen fibers
were significantly rearranged in the papillary and reticular
dermis, and elastotic material disappeared in the deep TCA
and phenol groups. At the same time, it was noticed that the
elastic fibers rearranged themselves. These positive histological
changes are more marked in the deep TCA and phenol groups
than in the other peel groups. As for the global effect, the study
shows an overall increase in dermal thickness with the deeper
peels.
In the long term, the histological changes brought about
by TCA are temporary when the TCA penetrates superficially
and long lasting when the TCA penetrates to the papillary der-
mis at least.
Dermal fibroplasia causes hypertrophic scarring, scar
adhesions, and keloids. Black or dark skins are more likely to
develop this type of reaction. The shoulder girdle and the lower
thorax are both high-risk areas, as is the jaw area on the face.
This type of scarring does not occur when necrosis goes no fur-
ther than the upper reticular dermis. Apart from a few excep-
tional cases (e.g., Ehlers–Danlos syndrome), the destruction of
the papillary dermis does not cause hypertrophic scarring.
There is a risk of skin atrophy when all of the appendages
of a treated area undergo necrosis. The skin does not have any
source of supply to regenerate cells quickly. The keratinocyte
clones can only come from the (distant) edges of the necrotic
areas; they cannot be produced in sufficient numbers for rapid
skin regeneration if the lesion is more than a few centimeters
in diameter. Lesions smaller than 1 cm in diameter, even in the
deep reticular dermis, do not pose a high risk of scarring unless
there is a secondary infection or the patient scratches the scabs.
Table 12.3  The Depths of Peelings, Type of Action, and Duration of Change
Level of destruction
Type of action
Duration of change
Upper stratum corneum
Exfoliation
Very temporary
Intraepidermal
Partial destruction of the epidermis
Very temporary
Basal layer
Destruction of the basal layer
Temporary
Grenz zone
Destruction of the Grenz zone
Medium duration
Papillary dermis
Destruction of the papillary dermis
Long lasting
Upper reticular dermis (with vertical fibers)
Destruction of the upper reticular dermis
Permanent
Deep reticular dermis (with horizontal fibers)
Destruction of the deep reticular dermis
Permanent; risk of scarring
Hypodermis
Scarring
Permanent

Trichloroacetic acid: GENERAL INFORMATION, TOXICITY, FORMULATIONS, AND HISTOLOGY      85
When all of the appendages have undergone necrosis, the
melanocyte reserve as well as the keratinocyte reserve suffers,
and scarring will be hypopigmented or unpigmented.
SELECTION OF THE RIGHT
TCA CONCENTRATION
Many books have been written about TCA in water application
techniques, and this book does not attempt to rewrite them.
Nevertheless, the author would like to point out a few impor-
tant details.
The main questions posed by new practitioners are: What
is the best TCA concentration? How many coats should be
applied? How often? How and when should I neutralize? These
are not simple questions, and providing simple answers would
give the appearance that selecting the right TCA concentration
is similar to inflexibly following an easy recipe.
The easiest of these questions to answer is about when to
neutralize. TCA action cannot be neutralized (see Chapter 3).
The best TCA concentration is, simply, the one we selected. The
point is to know how to select a TCA concentration and how to
calculate it.
In short, we are using chemical products, and we should
keep our calculations scientifically reproducible and accurate.
Only the w/w calculation makes sense for this point of view,
even if the w/v or the v/v is more common in the United States.
Doctors must select the right concentration for each
patient. Remember two points: First, a patient with thick skin
will need more acid than one with thin skin. Second, the most
important factor is the total quantity of acid that is able to inter-
act with proteins. A highly concentrated acid applied to thin
skin might burn it immediately, but the same concentration will
do a great job on thick, oily skin. Looking at the thickness of the
skin fold in the area of the malar bone gives us a simple clinical
appreciation of skin thickness: if the fold is 1 cm thick, the skin
is considered “normal”; if it is less than 1 cm, the skin is thin;
and if it is more than 1 cm, the skin is thick. Thin skin is more
sensitive to acids than thick skin, and remembering this fact
can help in selecting the TCA concentration.
However, transepidermal acid penetration does not
depend only on skin thickness; it also depends on the type of
acid. A “big” acid will penetrate faster than a “small” one—for
example, long fatty acids penetrate more slowly through the
skin than lactic acid.
Transepidermal penetration also depends on skin perme-
ability and prepeel skin conditioning. Thick oily skin,43 after
skin conditioning44 and acetone45 degreasing, can become as
permeable as thin skin. Skin dermabrasion (preferably using
3M wet or dry sandpaper 200) easily removes the stratum cor-
neum and largely deepens the action of the acids. The author
uses a complex technique called “anterior chemabrasion”
together with Easy TCA to treat acne scars and old atrophic and
deep stretch marks, with excellent results.
Another technique, that the author calls a “pixel peel,”
consists of multiperforating the stratum corneum using a
microneedling device (needles range from 0.25 to 2 mm), imme-
diately before applying a TCA peel. This technique is described
in Chapter 38.
Many actions can affect skin permeability. If the patient
scrubbed his or her face before the appointment, it will be more
permeable. Waxing the skin before the peel results in more
permeability. On the other hand, applying an oily moisturizer,
sunscreen, or a gel containing hyaluronic acid can reduce skin
permeability.
How many coats of TCA should be applied? Every practi-
tioner would like to have a clear, simple answer to this question.
Unfortunately, the number of coats depends on the permeabil-
ity of each patient’s skin and the TCA concentration of the solu-
tion. Focusing solely on the concentration is risky because there
are so many other variables to consider in determining how
many coats of the solution should be applied.
Two methods can be used to determine the number of
coats. The first one consists of guessing the right concentration
for a patient’s skin and hoping that the acid’s action will stop at
the right depth. The second one, which the author prefers, is to
use very few (three) different concentrations and apply several
coats until you see the desired frosting. This method results in
a peel to the desired level without the possibility of error.
Consider the following scenario. A phototype 2 patient
has skin of normal thickness and permeability and has under-
gone classic prepeel conditioning. The doctor would like to
reach the Grenz zone. He or she can decide to apply a 30% TCA
(w/w? w/v? etc.). What the doctor cannot decide is how deep
this acid will penetrate by itself. The doctor can rub the prod-
uct on the patient’s skin and see the result at the end, knowing
that more than one coat of a 30% w/w TCA solution on such
skin can be dangerous, or on the contrary can be insufficient.
The action of the acid solution can be seen, but only when the
damage is done and irreversible. This is why there are so many
reports of skin damage after TCA peels and why some authors
erroneously claim that TCA is not adapted to melasma treat-
ment. However, the results depend on the application tech-
nique and prepeel decisions. A 30% w/w TCA solution rubbed
once on normal thickness skin after prepeel conditioning usu-
ally results in a pink-white uniform frosting, showing a papil-
lary dermis penetration. The doctor surpassed the target of the
Grenz zone.
Another possibility for the same patient is to use a lower
concentration TCA solution, such as a 15% w/w solution. A
first coat induced only erythema. The doctor realizes that the
skin was less permeable than guessed and that he reached
the epidermal level only. When the patient’s skin has dried by
evaporation, the doctor will apply another coat of the same acid
solution. The skin will show small “frosting points,” and he will
deduce that the solution reached the basal layer depth. The next
coat will induce a cloudy frosting, a sign of the penetration of
the acids into the Grenz zone. When the doctor sees the cloudy
frosting, he stops the TCA solution application and knows that
the peel reached exactly the desired depth. Easy, isn’t it?
Usually, doctors focus on good prepeel conditioning
for better, more even penetration and faster regeneration.
Nevertheless, more attention should be paid to the immediate
postpeel event—the inflammatory reaction that begins imme-
diately after the first drop of acid contacts the skin.
This inflammatory reaction is necessary but also danger-
ous. A peel that induces no inflammatory reaction is not effi-
cient, because inflammation is the real skin rebuilding source.
At the same time, if this inflammation is uncontrolled, or self-
maintained, it begins a vicious cycle in which the free radicals
and the pro-inflammatory components liberated from cell
destruction induce more cell damage and more inflammation.
This inflammatory cycle is responsible for a lengthy stimula-
tion of melanocytes that will respond by synthesizing more
melanin and inducing PIH.

86      Textbook of Chemical Peels
Performing a peel can present a booby trap. You might
think that the pharmacist prepared a 30% mass by volume
(w/v) solution, but he prepared it w/w (which is stronger). Your
patient might have practiced virtual mesotherapy46 or a depila-
tion face wax the day before the peel; if so, the patient’s skin
will be permeabilized, acids will penetrate faster and deeper,
and an overpeel and side effects will result. The author avoids
these problems by using a safer and easier formula: Easy TCA
peel.47 This formula allows me to avoid the long and uncom-
fortable prepeel conditioning phase in the majority of cases48
because it can be applied using the progressive technique
explained above; it uses a specific postpeel mask, so I am able
to control the postpeel inflammatory reaction; and it will be
repeated once a week for 4 weeks. Each peel, performed up
to frosting points or maximum local frosting clouds, treats an
eventual pigment rebound induced by the preceding peel.
The Easy TCA postpeel mask is a complex formula con-
taining vitamins, trace elements, strong antioxidants, tretinoin
precursors, selenio-methionin, antityrosinases, and more. This
cream is applied once by the practitioner, immediately after the
desired frosting has been seen. It immediately scavenges free
radicals, stopping the excess inflammatory reaction and the
burning sensation induced by the Easy TCA peel solution. It
introduces into the skin elements that can help the skin regen-
erate faster and lowers the tyrosinase activity. Postpeel pene-
tration of ingredients is dramatically modified by the previous
application of the peeling solution. The postpeel rate of pen-
etration is much higher than the normal skin rate. The skin is
much more permeable during the postpeel period: sebum and
corneocytes no longer act as a barrier, and water soluble ingre-
dients can rapidly pass through this modified epidermis.
Large quantities of stimulating factors and antioxidants
can reach the dermis. It is clinically evident that the residual
inflammatory reaction is strong enough to stimulate the skin’s
rebuilding but not strong and long enough to stimulate mela-
nocytes or to slow down the basal layer regenerative sequences.
Some practitioners have wondered how this cream can imme-
diately stop the burning sensation if it is not a neutralizer (this
cream is not basic) and if the frosting signs continue to appear
normally, even after the postpeel mask has been applied.
Unfortunately, I cannot provide a scientific answer, but I have a
theory: the postpeel mask’s antioxidant properties are such that
they break the pro-inflammatory immediate postpeel reaction.
It is well known that inflammatory reaction typically is a major
component of pain.
To summarize, the Easy TCA formula offers many ben-
efits. It is easy to perform (10 minutes is the maximum time
needed for the face and neck), it is inexpensive, it is not pain-
ful (no anesthesia or painkiller is needed), it requires no skin
conditioning (the peeling solution and postpeel mask do the
work), it does not interrupt the patient’s social life (desquama-
tion looks like a sunburn), there is no phototype limitation
(phototypes 1–6 are allowed), and it presents few side effects
(an average 1.7% of transitory side effects, with duration less
than 8 days49). This peel, applied according to different proto-
cols, allows for a wide spectrum of depths of action and thera-
peutic indications, from active acne to pigmentations and acne
scars, photoaging, and old and deep stretch marks.50 It can be
applied to both the face and the body. Moreover, it can be per-
formed during the same session as other treatments, including
laser, intense pulsed light (IPL), mesotherapy, radiofrequen-
cies, depilation, botulinic toxin,51 surgery, and telangiectasies
treatment. Hyaluronic acid injections for wrinkle treatment are
even allowed, immediately before the Easy TCA peel.52
As mentioned earlier in this chapter, the author uses
three different concentrations of Easy TCA. The primary con-
centration, used on approximately 80%–85% of patients, is Easy
TCA solution containing vitamins, antioxidants, AHAs and
saponines, together with 15% w/w TCA. Advantages include
the postpeel mask’s protection against postpeel inflammatory
reactions and the ability to immediately stop postpeel burning.
Depending on the number of coats applied, the peel can reach
into the epidermis, basal layer, Grenz zone, or even the papillary
dermis. Papillary dermis peels require many coats of Easy TCA,
which may be uncomfortable for the patient. The author prefers
to use a derivative of Easy TCA to reach the papillary dermis:
Unideep.53 It has the same structure as Easy TCA; it consists of
a 23% w/w TCA and an adapted postpeel mask with the same
function as the Easy TCA. To go very deep into the skin to treat
focal old lentigine or solar keratoses, successive focal coats of
Easy TCA or Unideep can be applied, but the work is easier using
the Only Touch peel (OTP). It has the same qualitative base solu-
tion as Unideep but contains 45% w/w TCA. Only Touch has
no postpeel mask and has to be used in combination with Easy
TCA to avoid postpeel inflammation. Using OTP without Easy
TCA induces PIH in more than 60% of patients. When Only
Touch is done immediately before Easy TCA, the percentage of
PIH is lower: a maximum of 10% if the protocol is respected,
even lower if the patient does not scratch the scabs. OTP can
be used on small surfaces only; it is a focal peeling for treating
lesions whose diameter is than 1 cm. OTP is applied, avoiding
excess product, with a fine cotton bud or a wooden toothpick or
skewer. The practitioner should touch the lesion to be treated
quickly, precisely, and once only with the chosen applicator and
wait until the acid solution has dried completely. A significant
frosting will appear quickly on the face, and slowly on the body.
If no such frosting occurs, however, the practitioner can repeat
the application cautiously a few minutes after the solution has
dried. Immediately after the frosting occurs, apply the first of
the four basic protocols of Easy TCA on the entire treated area,
including the area where OTP has just been applied, to obtain
an even result and limit the risk of side effects.
OCCLUSION OF TCA
Following the example of phenol, it has been suggested that
occluding TCA could potentially enhance penetration. A his-
tological study by Stegman54 in 1980 revealed that occlusion
does in fact increase the depth of action of phenol but actually
reduces that of TCA.
An occlusive dressing applied quickly after a phenol peel
helps it macerate and deepens its action. An occlusive dressing
applied immediately after TCA creates a barrier to epidermal
water evaporation and to the water in the solution itself. Under
occlusion, this water accumulates in the uppermost layers of the
skin, where it dilutes the TCA fairly rapidly. With phenol, this
slight dilution enhances its penetration. An occlusive dressing
applied 30 minutes after TCA does not dilute the acid, as it has
had enough time to coagulate the proteins in the skin and neu-
tralize itself by combining with the proteins before occlusion
could dilute it.
Applying a greasy substance, such as Vaseline or an anti-
biotic ointment, immediately after a TCA peel is equivalent to
occlusion and can reduce the depth of necrosis caused by the
TCA.

Trichloroacetic acid: GENERAL INFORMATION, TOXICITY, FORMULATIONS, AND HISTOLOGY      87
INCREASING THE PERMEABILITY
OF THE STRATUM CORNEUM
The thicker the stratum corneum, the less the TCA penetrates,
and any method used to make the stratum corneum thinner
before applying TCA deepens its action. Applying tretinoin for
2 weeks before a TCA peel thins the skin and causes the kerati-
nocytes and corneocytes to dedifferentiate.
Acetone degreases the skin and causes chemical changes
in the membrane lipids, which increase the skin’s permeability
and the depth of action of the peels.
Applying a given concentration of TCA to thin and per-
meable skin will cause deeper necrosis than application to thick
and impermeable skin.
Another way of increasing the depth of skin necrosis is
to use higher concentrations of TCA, but this method produces
variable results because of the wide variation in penetration of
TCA in an aqueous solution. The risk of scarring increases with
the concentration of the TCA.
NOTES

1. The alpha carbon atom is that adjacent to the COOH group (as
with alpha hydroxy acids; see Chapter 6).

2. Which means that at a pH of 4.76, 50% acetic acid in an aqueous
solution is in the form of acetate.

3. “Glacial” acetic acid is 100% acetic acid. It is so called because of
its tendency to solidify near room temperature (its melting point
is 16.7°C).

4. Through the accumulation of lactic and/or glycolic acid. Tubular
necrosis develops rapidly.

5. Due to precipitation of myoglobin and oxalate crystals in the
renal tubules.

6. Bismuth Ch. Toxicologie Clinique. 5th ed. Paris: Editions
Médecine–Sciences, Flammarion, 2000.

7. Ketoacetic acid, oxoethanoic acid.

8. Oxalic acid (ethandioic acid) is HOOC.COOH, with pKa1 = 1.23
and pKa2 = 4.19.

9. Glycolic acid is HO.CH2.COOH, with pKa = 3.83 (see Chapter 6).
Glyoxylate is converted into glycolate by glyoxylate reductase.
10. Glycine (aminoacetic acid, aminoethanoic acid) is H2N.CH2.
COOH, with pKa = 2.4. It is transaminated by an alanine–gly-
oxylate aminotransferase. The glycine can then be incorpo-
rated into proteins and used for serine synthesis or simply be
degraded.
11. DCA was administered orally in the drinking water of rodents.
No specific data have been reported in humans.
12. Kitamura N, Ota Y, Mimura K. Effects of diisopropylamine
dichloroacetate on proliferation and differentiation of nor-
mal keratinocytes in vitro. Skin Pharmacology and Applied Skin
Physiology. 1999; 12: 317–325.
13. Johnson K, with the Canadian Task Force on the Periodic Health
Examination. Periodic Health Examination, 1995 update: 1.
Screening for human papillomavirus infection in asymptotic
women. CMAJ. 1995; 152: 483–93.
14. Although using the new phenol formulas seems to be safer (see
Chapter 36).
15. TCA is often found in drinking water as a by-product of
disinfection.
16. Obtained by simple dilution of TCA crystals in water.
17. The author begs any chemist reading this to forgive this explana-
tory shortcut.
18. Trauchessec JM, Pissot F. Solution d’acide trichloracétique
masse par masse pour peelings dermatologiques, nécessité
d’une formulation explicite pour les solutions d’acide trichlora-
cétique. 18th réunion du GRCD, Perpignan, 9 Septembre 1995:
28–38.
19. Trauchessec JM, Pissot F. Solutions d’acide trichloracétique
masse par masse pour peelings dermatologique. Les Nouvelles
Dermatologiques. 1996; 15: 252–55.
20. One apple plus one apple equals two apples, whereas one apple
plus one pineapple equals two pieces of fruit.
21. According to Roenigk, applying TCA at 70% m/v on the face
usually causes scarring, while in gynecology, treating vaginal or
cervical condylomas does not produce any scarring. McCollough
EG, Langsdon PR, Maloney BP. Chemical Peel with Phenol.
Roenigk RK, Roenigk HH (Eds.). Dermatologic Surgery, Principles
and Practice. 2nd ed. Oxford: Marcel Dekker, 1996: 1147–60.
22. Rereading the textbooks that I used at the beginning of my career
as a “peeler” makes me realize why it was so difficult to get an
overall grasp of the field and to understand the consistency of
the technique.
23. Brody H, Stegman S. Histological study by Harold Brody and
Samuel Stegman, at 3, 30, and 90 days.
24. TCA therefore does not have an “all or nothing” action.
25. McCollough EG, Langsdon PR, Maloney BP. Chemical Peel
with Phenol. In: Roenigk RK, Roenigk HH (Eds.). Dermatologic
Surgery, Principles and Practice. 2nd ed. Oxford: Marcel Dekker,
1996: 1147–60.
26. Easy TCA and Unideep consist of peel solutions as well as a post-
peel cream whose ingredients help achieve better results and
avoid complications. Only Touch consists of a solution alone but
has to be combined with Easy TCA or Unideep, and thus benefits
from the application of the postpeel cream of these peels as well.
27. Chiarello SE, Resnik BI, Resnik SS. The TCA masque. A new
cream formulation used alone and in combination with Jessner’s
solution. Dermatological Surgery. 1996; 22: 687–90.
28. Vergereau R, Trauchessec JM, Peyronnet B. Le new peel. Le
Journal de Médecine Esthétique et de Chirurgie Dermatologique. 1990;
XXII (68): 243–55.
29. See the many previously published works on the semiology of
TCA–SAS peels.
30. See Chapter 2.
31. Peyronnet B, Trauchessec JM, Vergereau R. Le peeling doux. Le
Journal de Médecine Esthétique et de Chirurgie Dermatologique. 1991;
XXIII (69); 33–37.
32. In fact, the commercially available “glyceryl monooleate” is a
mixture of esters of glycerol with a number of fatty acids (long-
chain carboxylic acids), the major component of which is the
monoester with oleic acid.
33. TCA Masque, Accu Peel cream, and TCA cream peel.
34. From the Greek chele, meaning “claw.”
35. Cabaní I. Nuestra experiencia en la aplicación de la nueva más-
cara de TCA. Medicina Estética (SEME). 1995; 39: 25–29.
36. A clay is a friable sedimentary rock that can be molded when
soaked in water.
37. Thanks to the metallic cations of the crystalline lattice.
38. Thanks to the oxygen atoms of the silica molecules.
39. Which would be pointless—even dangerous—if the TCA mask
at 20% had the same effect as 50% TCA.
40. Prior application of a glycolic acid mask, and close and difficult
monitoring of the contact time and downtime are necessary.
41. McCollough EG, Langsdon PR, Maloney BP. Chemical Peel
with Phenol. In: Roenigk RK, Roenigk HH (Eds.). Dermatologic
Surgery, Principles and Practice. 2nd ed. Oxford: Marcel Dekker,
1996: 1147–60.
42. Butler P, Gonzales S, Randolp M, et al. Quantitative and quali-
tative effects of chemical peeling on photo aged skin: An
experimental study. Plastic and Reconstructive Surgery. 2001; 107:
222–28.
43. Skin fold = more than 1 cm.
44. Glycolic acid to reduce stratum corneum thickness + tretinoin
for stimulating basal layer turnover and regeneration and for
reducing the stratum corneum permeability: this kind of prepeel
conditioning makes the skin much more permeable.

88      Textbook of Chemical Peels
45. Note that acetone not only degreases the skin but also begins a
protein denaturation that makes the skin more permeable.
46. Virtual mesotherapy: slight abrasion using sandpaper, applica-
tion of specific vitamins and other elements to the skin, use of
Excellderm (nonthermogenic radiofrequencies for inducing an
intracellular penetration). See
47. See this book or
48. I would use a prepeel conditioning only in specific cases, such
as for a phototype 4 or 5 patient with a long history of familial
melasma.
49. Unpublished statistic established from a total amount of 5,000
peeling sessions in Clinica Hera, Empuriabrava, Spain: 28 transi-
tory, easy-to-treat side effects. No definitive side effect.
50. See: left column, treatment tips, peelings, for
a complete description of active acne, stretch mark, and melasma
treatments, along with the protocol for local phenol peels around
the eyes and lips.
51. Ten minutes after botulinic toxin injection, Easy TCA (as a basal
layer peel) can be performed. The author has never seen migra-
tion or shorter results after this association.
52. The author also read the HA notice for injection, which stated
not to perform peelings after HA injections. Nevertheless, this
recommendation is valid only because of the huge release of free
radicals after usual peelings. Free radicals rapidly damage the
HA polymer, breaking it and shortening its life. The Easy TCA
postpeel mask scavenges free radicals at the same time they are
produced, which can stop self-maintained free radical reactions
that may damage the HA polymer.
53. Easy TCA, Unideep, and Only Touch are peels developed by
Skin Tech, based on the author’s formulas.
54. Stegman SJ. A study of dermabrasion and chemical peels in an
animal model. Journal of Dermatologic Surgery and Oncology. 1980;
6(6): 490–97.

13
Trichloroacetic acid
Indications and contraindications
MAIN INDICATIONS FOR
TRICHLOROACETIC ACID
Trichloroacetic acid (TCA) is an extremely versatile peel that
can reach all depths and can be applied to all skin types, on all
parts of the body and in many indications. Using solutions that
are properly prepared and following strict protocols ensures a
safe and effective peel. Repeating several easy peels, such as
Easy TCA, can boost collagen and elastin production to the
same degree as a deeper peel; repetition may even be preferable
to using a more aggressive peel when the aim is to stimulate the
skin and renew the epidermis, as is the case in the treatment of
photoaging.
On the other hand, when the desired effect is destruction
of deeper layers of the dermis and epidermis to eliminate cer-
tain lesions, a single deeper peel may be a better indication than
repeating several peels to the Grenz zone, as is the case when
treating lentigines and mixed or dermal melasma.
Folds and Wrinkles
Deep wrinkles and folds are not a good indication for TCA
peels:
•
Folds cannot be treated by peels and require surgery, der-
mal fillers, or thread lifts. Deep nasolabial folds and mari-
onette lines do not always respond to phenol.
•
Dynamic wrinkles respond well to a combination of bot-
ulinum toxin and peels: the peels restructure the epider-
mis and the dermis on an unmoving base and the clinical
results are better when these two treatments are combined
than when used alone.
•
Fine sun-related wrinkles respond well to TCA, but deeper
ones respond better to phenol.
•
Wrinkles around the mouth and eyes are very poor indica-
tions for TCA, even in high concentrations; phenol is far
more effective (see Chapter 36).
Photoaging
Early photoaging (Figure  13.1) is one of the best indications
for a TCA peel. In short, it improves and evens out the com-
plexion, reduces or eliminates lentigines, improves elastosis
and fine lines, improves skin tone, and generally brightens the
skin. TCA peels have often been combined with tretinoin in
this indication (see Chapter 2). Photoaging on the hands is an
excellent and easy indication for TCA (see the next section and
Figure 13.3).
Solar Elastosis
The papillary dermis is sometimes so atrophic that the epider-
mis appears to be lying directly on the middle dermis, with-
out the intervening Grenz zone. The epidermis then becomes
“too big” for the underlying dermis, and wrinkles appear—like
baggy clothes that crease on a body that has grown too thin. In
theory, only a very deep peel can treat solar elastosis, by produc-
ing enough good-quality collagen and elastin in the papillary
dermis to fill the atrophied dermis and bury the sun-damaged
fibers deep down (see Chapter 26). Repeating certain types of
peel to the Grenz zone1 once a week may be effective enough to
improve the appearance of the skin without the downtime that
inevitably follows medium or deep peels. Of course, the deeper
peels will be more effective; there is no comparison between
the results of a phenol peel and those of an alpha hydroxy acid
(AHA), resorcinol, or TCA peel!
On the other hand, dermatologically and toxicologi-
cally, phenol is a risky option for treating anything but facial
skin. Body skin only benefits from other agents. Solar elasto-
sis appears in several forms. It starts with the appearance of
limited areas of elastosis that as yet have no or little clinical
expression. Its maximum expression is seen when the skin has
a cobblestone appearance (Figure 13.2). The type of treatment
depends on whether the elastosis is in its very early stages
or if it is more advanced (Figure 13.2). Early elastosis, which
is characterized by very fine lines and an uneven complexion,
can be treated successfully with four Easy TCA peels or one
Unideep peel, while advanced elastosis can only benefit from a
deep reticular peel (full-face Lip & Eyelid Formula) and a major
restructuring of the skin. TCA would have no effect on the deep
wrinkles in Figure 13.2, no matter which concentration, adju-
vants, or other combined treatments were used.
Solar elastosis often affects the legs if they are frequently
exposed to the sun, which is the case with women who wear
skirts. The skin between the knee and the malleolus is some-
times affected by visible elastosis that can be improved by com-
bining abrasion and Easy Phytic solution (see Chapter 11). The
hands and forearms respond extremely well to Easy TCA, with
no side effects (Figure 13.3).
Lentiginosis2
TCA is effective in treating solar lentigines. The concentration
of the TCA is chosen depending on the assumed depth of the
lentigo. Relatively superficial lentigines are easily treated with
Easy TCA (Figure 13.4). Lentigines of medium depth respond
to Unideep. Lentigines originating from the deepest dermal
papillae and embedded deep in the dermis only respond to
very concentrated TCA (Only Touch), or even phenol (Lip &
Eyelid Formula), applied locally and combined with Easy TCA
(or Unideep) to even out the results and treat the smaller sub-
clinical lesions (Figure 13.5). It should be noted that a TCA peel,
even to the papillary dermis, does not always treat lentigines
definitively and that several peels to the papillary dermis may
be necessary for long-term results.

90      Textbook of Chemical Peels
Perioral Wrinkles
Very fine lines around the mouth can be improved by a com-
bination of filling techniques (e.g., hyaluronic acid) and one
or more TCA peels to the papillary dermis, but the results
achieved with TCA never equal or even come anywhere near
those achieved with phenol, which is preferred in chemical
labioplasty or cheiloplasty (see Chapter 36) in combination
with botulinum toxin, if possible.
Prevention of Skin Aging
The wisest patients go to see their doctor before the clinical
signs of aging appear and seek advice on how to prevent skin
aging. The preventive treatments that might be suggested to
Figure 13.1  Early photoaging: a good indication for TCA.
Figure 13.2  Solar elastosis (skin with a cobblestone appear-
ance): this is not the best indication for TCA.
(a)
(b)
Figure 13.4  Lentiginosis and photoaging. (a) Before treatment,
there are about 40 lentigines and/or actinic keratoses. (b) After four
sessions of Easy TCA peels to the Grenz zone, there are only about
10 lentigines/keratoses left. The signs of photoaging are visibly
reduced: fine lines, quality of the skin, improved eyelid tension, etc.
Figure 13.3  Overall rejuvenation of the hands after four sessions
of Easy TCA at a rate of one session every 2 weeks.