The Art of Aesthetic Surgery Principles and Techniques Three Volume Set Second Edition

One consideration for sensitive skin applies to any treatment: when recommending
or prescribing new products to a patient with sensitive skin, especially one who has
a tendency to develop contact dermatitis, the physician should instruct the patient
to test the new product for its allergenicity potential by applying it in the cubital
area two times a day for 5 consecutive days. If by day 5 the patient does not develop
contact dermatitis, the product should be safe for use on the face.
Evidence-Based Skin Care Musts:
Retinoids and Sunscreens
As physicians it is our ultimate goal to recommend evidence-based and scientifically
supported treatments. Unfortunately, when it comes to skin care and cosmetic prod-
ucts, this is a difficult task. There are only two treatments or substances whose use
and biologic effects are backed by good scientific data: retinoids and sunscreens.
The sine qua non of any skin care regimen is the daily use of a sunscreen. In addi-
tion, as soon as the aging process starts and becomes a concern, daily application of
a topical retinoid is advised. The use of topical antioxidants is also recommended,
although currently there is less evidence of its efficacy from well-designed clinical
trials than the other two products.
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Cosmeceuticals
The cosmetic skin care market, especially products intended to reduce the effects of
aging, is a multibillion dollar business. New products with new ingredients are con-
stantly being developed. The sole purpose of “simple” cosmetics is to clean, smooth,
and beautify the skin. Not much harm can be done with such products, and their
purpose is well defined. However, this is not necessarily the case for another cate-
gory of cosmetic products, called cosmeceuticals.
More and more biologically active ingredients are being included in cosmetic prod-
ucts that are not sold only for a beautifying purpose, but that claim truly biologic
effects, such as photoprotection, antiwrinkling, antiaging, and skin tightening. These
products all fall into the category of cosmeceuticals.
The term cosmeceuticals was first introduced by dermatologist Albert Kligman two
decades ago. Today cosmeceuticals represent the fastest-growing segment of the skin
care market. Cosmeceuticals constitute an intermediate between cosmetics and drugs
(hence cosme from cosmetics and ceuticals from pharmaceuticals). In contrast to
regulated drugs, these products are not sold for therapeutic purposes, but rather for
cosmetic reasons. Thus cosmeceuticals are not regulated by the U.S. Food and Drug
Administration (FDA) and consequently are not required to undergo the same rig-
orous premarket testing as do drugs. Unfortunately, this has led to a situation in
which most cosmeceuticals manufacturers can claim various biologic effects for their
products. Most cosmeceuticals lack large-scale, randomized, blinded, controlled clini -
cal trials or long enough follow-ups to assess their actual biologic properties. Cosme -
ceutical manufacturers today assert that their products produce antioxidant, photo -
protective, antiinflammatory, and collagen-stimulating effects. A vast array of
cosmeceutical products claim antiaging and antiwrinkle activity.
Usually cosmeceuticals do show some effect in vitro. However, in vitro success does
not prove in vivo efficacy. In vivo clinical trials of the final formulation are rare. An
active compound might perform miraculously in vitro, or even in an in vivo animal
model. However, when incorporated into the final formulation with preservatives
and fragrances, there are many factors that might influence and change the active
compound’s biologic activity. Furthermore, for the active compound to penetrate
through the stratum corneum, be absorbed into the skin, retain its stability, and stay
at the specific structure long enough to exert its biologic effect requires complex
processes that cannot be guaranteed by any in vitro data. Thus, even for an expert
cosmetic physician, it is very difficult to assess a product’s true biologic effects.

BASIC SKIN CARE
A Regimen for Any Skin Type and at Any Age
Cleansing
Cleansing the skin is the first step in every skin care regimen and should be routinely
performed every morning and evening, regardless of an individual’s skin type or age.
The purpose of cleansing the skin is not only the removal of dirt, microorganisms,
makeup, and other pollutants, but also the removal of desquamated cells from the
skin surface. This allows skin to better absorb other topical therapies and aids in a
constant rejuvenation process.
Using water alone for cleansing will remove roughly 65% of dirt and oil from the
skin. However, water alone will not remove the oils from makeup and environmen-
tal pollutants.
To remove sebum and dirt, skin cleansers have to lower the surface tension of the
skin. With this in mind, surface-active substances, the so-called surfactants, have to
be added to skin care products. Surfactants represent the key active ingredient in
cleansing formulations. They are also crucial components that influence a cleanser’s
degree of mildness or irritancy. The type of surfactant used varies by the type of
cleansers, such as bars and liquids.
The main problem associated with the use of cleansers is a potential weakening of
the stratum corneum by the surfactant’s removal of the lipids required for the struc-
ture of the epidermis. When this occurs, the skin barrier is disrupted, leading to a
disturbance in moisture level, a change in the skin’s surface pH, and ultimately irri-
tation to the skin.
Fortunately, cleansing technology has evolved greatly within the past two decades. At
one time basic soap was used, which ultimately led to the introduction of synthetic
detergent–based bars or liquids (the so-called syndets), which are non–soap-based
surfactants. This has greatly helped to reduce the damaging effect of skin cleansers.
Today most products recommended by aesthetic physicians are syndet cleansers.
Some cleansers can lead to immediate after-wash tightness, dryness, pruritus, and
erythema. It is known that harsh surfactants, especially those contained in soap-
based products, interact with proteins and lipids within the skin, which can lead to
skin dryness, irritation, scaling, and roughness. Furthermore, a cleanser’s pH plays
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an integral role as to whether it will irritate the skin or damage the stratum corneum.
Soap-based cleansers not only contain harsh anionic surfactants but also are alka-
line and thus raise the pH of the skin, whereas syndets are mostly neutral or slightly
acidic. Because of their pH, they remove less intracellular lipid. Various studies have
shown a higher irritation potential for soap-based cleansers compared with cleansers
with syndets.
Besides the main component of a cleanser (surfactants), these products contain var-
ious compounds, such as binders for stabilization of the formulation, sensory mod-
ifiers, fragrances, and preservatives. In addition, moisturizers (emollients and humec-
tants) are now added to many cleansers; these help to maintain the hydration status
and barrier function of the skin.
A cosmetic patient with an ideal skin care regimen will also apply some kind of top-
ical retinoid to the skin. Although potentially helpful for collagen formation, retinoids
may also weaken the skin barrier, making the skin prone to irritation. Many of the
regularly performed cosmetic procedures, such as chemical peels and laser proce-
dures, intentionally lead to an impaired stratum corneum. Hence the cleanser of
choice for a cosmetic patient should be mild, nonirritating, fragrance free, noncome-
dogenic, and moisturizing so that it will not further exacerbate the already compro-
mised skin barrier from other treatments.
Currently marketed cosmetic cleansing products for the face include soaps, super-
fatted soaps and beauty bars, dermatologic bars and liquid cleansers, lipid-free
cleansers, syndet cleansers, and cleansing creams. Nonfoaming cleansers with no or
a low level of surfactants are in general milder and less irritating than foaming
cleansers, which contain surfactants. However, all nonfoaming cleansers are some-
what less efficient in cleansing. The lowest irritation potential will be provided by a
cleanser that contains both nonionic/silicone-based surfactants and moisturizers.
The best currently available choice of cleanser for cosmetic patients is a liquid fa-
cial cleanser. These cleansers have an acidic pH, mostly contain moisturizers, and
show a high “rinsibility.”
Patients with dry skin types should avoid foaming cleansers and use oil-based, mois-
turizing cleansers that are marketed as the following:
 Cleansing creams
 Cleansing milks
 Cleansing lotions
 Cleansing oils
 Hydrating cleansers
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Patients with oily skin should avoid these cleansing types and use foaming or gel-
based cleansers. Patients with aging skin that is not too sensitive or dry can inter-
mittently use cleansers that contain glycolic acids. Although potentially irritating,
such cleansers will increase desquamation and provide a mild antiaging effect.
Moisturizing
A 2004 study by Feldman and colleagues showed that after hydrocortisone (27.6%)
and antiinfectives (23.4%), moisturizers (13.4%) are the third most commonly rec-
ommended over-the-counter topical product. Moisturizing the skin is a crucial com-
ponent of every skin care regimen, not just for dry skin, which has been shown to
have low levels of moisture. Moisturizers are helpful when there is a disturbed epi-
dermal barrier with increased transepidermal water loss and thus a reduced water
content in the epidermis. Skin can only be moisturized when the stratum corneum
is intact, which allows the skin to trap the water in the dermis and viable layers of the
epidermis. Too little water content in the skin will lead to dry skin with roughness,
flaking, and irritation.
The goal of moisturizers is to increase the moisture level (that is, the water content
in the stratum corneum), to provide a protective film, and to cover tiny disruptions
in the skin while restoring the skin barrier function. Ultimately, this further reduces
moisture evaporation from the skin, maintains the hydration level, and leads to both
a smoother appearance and increased tactile properties of the skin. This can be
achieved in various ways:
 By promoting water retention within the stratum corneum using humectants
 By minimizing water evaporation from the skin using occlusives
 By increasing the integrity of the skin barrier using occlusives
Emollients complement activity of the occlusives and aid in smoothing the surface
of the skin. Most moisturizers contain all three components—humectants, occlu-
sives, and emollients—in varying combinations.
Humectants
Humectants are water-soluble, hygroscopic materials with high water-absorption
capabilities; they increase the ability of the stratum corneum to hold on to water by
attracting and enhancing the water absorption from the dermis into the epidermis.
In high-humidity conditions (atmospheric humidity greater than 80%), water can
also be absorbed from the external environment into the stratum corneum. The rea-
son moisturizers are formulated to combine humectants with occlusives is to pre-
vent the enhanced water absorption from the dermis into the epidermis from being
lost by increased transepidermal water loss.
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By drawing water into the skin, humectants lead to a swelling of the stratum
corneum, which smooths out fine lines and wrinkles. Many manufacturers of mois-
turizers use this phenomenon to claim antiwrinkle properties, although these prod-
ucts do not impart these effects long term.
The most effective humectant is glycerol (glycerin). Other commonly used humec-
tants include propylene glycol, gelatin, natural moisturizing factor (NMF), urea, pan-
thenol, sodium, sorbitol, and sodium hyaluronate. One of the newer and widely mar-
keted humectants is hyaluronic acid. Many products containing hyaluronic acid
claim its antiwrinkle activities, but as explained earlier, this effect is solely based on
drawing water into the skin.
Occlusives
Occlusives are oily substances that reduce transepidermal water loss to the external
environment by creating a hydrophobic barrier over the skin, supporting the lipid
matrix between the keratinocytes, and thereby increasing the integrity of the skin
barrier. Substances with occlusive effects include fatty acids (linoleic acid, lanolin), oils,
waxes and wax esters (mineral oil, paraffin, petrolatum, silicone derivatives, squa-
lene, beeswax), phospholipids, and sterols. Two of the best occlusives commonly
used are mineral oil and petrolatum. Reduction in transepidermal water loss by
petrolatum is 99%, and by mineral oil 50%. Oil-free occlusives include silicones
such as dimethicone.
There is a subset of individuals with sensitive skin and a tendency for allergic reac-
tion who develop contact sensitization to lanolin. Patients with known contact al-
lergies should use moisturizers without lanolin. An example might be a moisturizer
containing petrolatum, for which virtually no contact dermatitis has been reported.
Emollients
Emollients are mainly oils and lipids that help to hydrate the skin by filling the gaps
between desquamating keratinocytes, leading to an increased cohesion of the cor-
neocytic skin barrier. Emollients improve the appearance of the skin, increasing
smoothness, softness, and flexibility, resulting in greater light refraction and more
even-looking skin. There are various types of substances available with emollient
properties. These include astringent emollients (such as dimethicone), dry emollients
(isopropyl palmitate), fatting emollients (castor oil, jojoba oil, propylene glycol), and
protective emollients (isopropyl isostearate). Various emollients, such as petrolatum,
lanolin, and mineral oil, also possess humectant and occlusive properties.
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The majority of moisturizers are either creams, which are water-in-oil emulsions, or
lotions, which are oil-in-water emulsions. There are also more complex formula-
tions available, such as serums and gels.
Creams are richer and tend to include heavier lipids. Typically creams contain min-
eral oil, petrolatum, lanolin, and water. Lotions are thinner, and in general, contain
water, mineral oil, and propylene glycol.
Patients with dry skin need to apply a moisturizer at least twice a day, in the morn-
ing and in the evening. In dryer, less humid environments or in winter, a repeat ap-
plication during the day might be needed. Ideally, creams are applied at night, whereas
lotions can be applied during the day. Patients with markedly dry skin, or in dry cli-
mates, might need to apply cream in the morning as well. Moisturizers exert their
most pronounced effect when they are applied on slightly dampened skin.
Patients with oily skin might not feel the need to apply moisturizer at all. However,
no skin type is static; there are situations in which skin that is usually oily might
tend to be drier and thus require a moisturizer. Ideally, patients with oily skin should
apply the lighter lotions or even gels. Silicone derivatives in particular are targeted
for those with oily skin.
The ideal moisturizer is noncomedogenic, nonirritant, fragrance free, hypoallergenic,
and nonsensitizing. Patients with sensitive skin should choose this type of product.
Today newer moisturizers contain additional, mostly active ingredients, such as an-
tioxidants, retinoids, and sun protectants. These moisturizers often claim to have
additional effects, such as photoprotectant, antiaging, and sun protectant proper-
ties. Such products clearly belong in the category of cosmeceuticals. This antiaging
technology is the fastest-growing segment of the facial moisturizer market.
Many moisturizers intended for use during the day contain a sun-protection factor
(SPF). In general, the SPFs contained in daytime moisturizers are somewhat low (SPF
12, 15, or 20). Patients using these moisturizers should also apply sunscreen with
an SPF 30 on top of the daily moisturizer. Moisturizers intended for nighttime and
antiaging use will also often contain over-the-counter retinoids (retinol or retinalde-
hyde). These are excellent options to introduce the use of a topical retinoid to a pa-
tient’s skin care regimen. (This is described in more detail on pp. 283 to 286.)
Protection
Photoprotection
Research over the past 40 years has made the association between sun exposure,
photoaging of skin, and skin cancer indisputable. It has been clearly demonstrated
that UV radiation causes skin aging. More important, UV light is now accepted as
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the main etiologic factor in the development of cutaneous malignancy. In the United
States, as reported by Ibrahim and Brown, 50% of all malignancies are attributable
to skin cancer, and the increased rates of incidence of nonmelanoma skin cancer, as
well as melanoma, are the fastest growing rates for any malignancy.
UV light can be divided into UVA (320 to 400 nm), UVB (280 to 320 nm), and UVC
(190 to 280 nm). UVA and UVB rays are the clinically relevant radiation, because UVC
rays are filtered by the ozone layer in the stratosphere. Acute effects of UV radiation
on the skin include inflammation, erythema, sunburn, and pigmentation (tanning).
Chronic irradiation with UVA and UVB leads to cutaneous immunosuppression, pho-
toaging, and photocarcinogenesis. It seems that induction of inflammation and loss of
skin elasticity can even be induced by suberythematous doses of UV radiation.
The clinical effects of sun exposure on photoaging can be easily visualized when
comparing sun-protected body sites with sun-exposed ones. Photoaged skin shows
remarkably more clinical changes than sun-protected, chronologically aged skin,
such as sallowness, roughness, wrinkles, mottled pigmentation, telangiectasia, and
various benign and malignant neoplasms.
Photoprotection is an essential prophylactic and therapeutic element to combat the
deleterious cutaneous effects of UV radiation and to prevent and slow the signs of
cutaneous aging. Photoprotection goes beyond skin care: in addition to sunscreens
conferring photoprotection, sun-avoidance and protective clothing can add signifi-
cantly to safeguarding the skin from damaging UV radiation.
Sunscreens
Data show that protection of the skin with sunscreen can reduce the development of
skin cancer and inhibit photoaging. There have been tremendous developments in the
sunscreen industry. In contrast to Europe, where sunscreens are regarded and treated
as cosmetics, the FDA regards sunscreens as drugs and requires rigorous clinical tri-
als before regulatory approval. This explains why certain sunscreen filters only enter
the U.S. market after they have already been used in Europe for many years.
The SPF rating is used almost universally. However, SPF is primarily an indicator of
protection from UVB rays, and the protection provided from the effects of UVA is
somewhat difficult to estimate. In fact, commercially available sunscreens will pro-
vide reliable protection against UVB rays, whereas many of them will not be equally
effective against UVA rays. SPF is defined as the UV dose (mainly UVB) required to
develop a minimum erythema dose (MED) after the application of 2 mg/cm² of sun-
screen. Hence an SPF 2 absorbs 50% of UV radiation and will allow a patient to
stay in the sun double the time before developing erythema, as compared with the
same patient who has not used the sunscreen.
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With regard to UVA rating, the FDA recently proposed a new four-star grading sys-
tem and a description (low, medium, high, and highest). The rating system includes in
vitro and in vivo measurements and will be based on measuring the sunscreen’s abil-
ity to reduce the penetration of UVA rays into the skin as well as to prevent tanning.
There are two different types of filters used in sunscreens: organic, also known as
chemical filters, and inorganic, or physical filters/blockers.
Organic or Chemical Filters
Organic filters act by absorbing UV radiation and then emitting the absorbed en-
ergy as heat. They can be divided into UVA, UVB, and dual UVA/UVB or broadband
filters. There are various filters with differing absorption spectra. To protect the skin
over the entire UV spectrum, different filters may be combined in the same product.
UVB filters include para-aminobenzoic acid (PABA) and derivatives, cinnamates and
salicilates. UVA protection was revolutionized with the introduction of butyl
methoxydibenzoylmethane (avobenzone); it was the first organic filter that provided
some UVA protection. Recently, development has gone toward broadband UVA and
UVB filters with the introduction of ecamsule (terephthalylidene dicamphor sul-
phonic acid, Mexoryl SX), dometrizole trisiloxane (Mexoryl XL), and bemotrizinol
and bisoctrizole (Tinosorb S and Tinosorb M). Chemical sunscreens can induce con-
tact dermatitis in susceptible individuals. Such compounds include benzophenone,
avobenzone, and PABA.
Inorganic or Physical Filters
Inorganic filters, also called physical blockers, are made of sizable particles that re-
flect and scatter UV and visible light. The two most widely used inorganic filters are
zinc oxide (ZnO) and titanium dioxide (TiO2). Another inorganic filter used is iron
oxide. Depending on the particle size, such blockers not only reflect and scatter light,
but absorb it as well.
The main problem with sunscreens containing inorganic filters is that they tend to
leave a whitish discoloration and film on the skin, which is cosmetically disturbing.
Newer formulations attempt to overcome this problem by the process of microniza-
tion; that is, producing smaller-sized particles, which results in less scattering of vis-
ible light and thus less opaque discoloration.
Currently there are no documented reports of sensitization reactions to physical fil-
ters. Thus inorganic sunscreens are the best choice for patients with sensitive skin
who have a tendency to develop contact dermatitis.
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Patients should be instructed to use sunscreen every day of the year, whether the sun
is shining or not. Sunscreens should be applied in the morning 30 minutes before
leaving the house. All sun-exposed areas should be treated. Patients should develop
the habit of reapplying sunscreen at midday.
In our opinion, a daily sunscreen should ideally contain an SPF 30 and should pro-
tect from UVA radiation as well. When extended sun exposure is planned, such as
on weekends and holidays, an SPF 50 and high UVA protection may be consid-
ered and applied on all exposed areas of the body.
Patients with dry skin should use cream formulations to moisturize the skin. Patients
with oily skin should use lotions or gels, since they are lighter than creams. Patients
with sensitive skin will ideally use sunscreens with physical filters and avoid sun-
screens with chemical filters, such as avobenzone, benzophenone, and PABA.
Patients with such pigmentary disorders as melasma, lentigines, and postinflamma-
tory hyperpigmentation, which are known to worsen on sun exposure, should use
an SPF 50 and high UVA protection every day without exception.
Patients should be advised that a preexisting or acquired tan does not protect the
skin from the sun and thus “pretanning” before going on vacations will only add to
increased sun damage. Studies have shown that the photoprotection given by an
acute suntan is only equivalent to a sunscreen SPF 2 to 3.
Because antioxidants are known to be photoprotective and lessen ROS-induced sun
damage, newer sunscreens include antioxidants, such as vitamins C and E, green tea
polyphenols, and resveratrol. However, such antioxidant sunscreens are less potent
than physical filters in preventing sunburn.
A Regimen for the Prevention
and Treatment of Skin Aging
Retinoids
Topical retinoids, together with sunscreens, are the fundamental agents used in top-
ical cosmetic therapies. The term retinoid is used as a generic chemical term that en-
compasses the naturally occurring compounds with vitamin A activity, as well as the
synthetic derivatives of retinol (retinoic acid). All retinoids exert their biologic ef-
fects by engaging and activating nuclear receptors.

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Retinoids are classified into various generations, such as naturally occurring first-
generation retinoids and synthetic or second- through fourth-generation retinoids.
The classic indication for the use of a retinoid is acne. The first anecdotal evidence
supporting the positive effects of retinoids on photodamaged and photoaged skin
was observed in a study performed by Kligman et al in 1986, when he treated fe-
male acne patients with topical tretinoin. The patients commented that their skin
felt smoother and less wrinkled. Histologically, a replacement of the atrophic epi-
dermis by hyperplasia, an elimination of dysplasia and atypia, an eradication of mi-
croscopic actinic keratoses, a uniform dispersion of melanin granules, and new col-
lagen formation in the papillary dermis, as well as exfoliation of retained horn in
the follicles were all noted. These data led to the conclusion that topical tretinoin is
at least partly capable of reversing the structural damage of excessive UV exposure
and may be useful in decelerating the photoaging process. Other studies followed,
which ultimately resulted in FDA approval of tretinoin for the treatment of photo-
damaged skin.
Subsequently various double-blind placebo-controlled trials have demonstrated that
the topical application of retinoids can lead to improvement in global appearance,
reduction of fine lines and coarse wrinkling, improvement of skin texture, and re-
duction of roughness, pigmentation, and sallowness. Most of the available studies
documenting the effects of topical retinoids on photodamaged skin are on the ef-
fects of tretinoin, with significantly fewer data on the other retinoids.
Generations of Retinoids
First-generation (nonaromatics)
Retinol
Retinaldehyde
Tretinoin
Isotretinoin
Alitretinoin
Second-generation (monoaromatics)
Etretinate
Acitretin
Third-generation (polyaromatics)
Adapalene
Tazarotene
Arotinoid
Fourth-generation (pyranones)
Seletinoid G

Tretinoin
As previously discussed, the benchmark product for use in photodamaged skin—
and currently the only FDA-approved topical retinoid for that specific indication—
is tretinoin. Tretinoin is available in various concentrations from 0.01% to 0.25%
and a variety of different formulations (creams and gels). The drawback of tretinoin
is its irritation potential. If not instructed properly on the mode of application, pa-
tients can develop retinoid dermatitis with scaling, erythema, pruritus, and stinging.
Retinol and Retinaldehyde
Retinol and retinaldehyde are popular retinoids included in over-the-counter prod-
ucts. They have both been shown to be less irritating than tretinoin but still confer
some degree of efficacy against photodamage.
Retinyl Palmitate and Retinyl Acetate
The esters retinyl palmitate and retinyl acetate can be found in various cosmeceuti-
cals. However, they are not considered topically effective against photoaging.
Isotretinoin
Isotretinoin is a prescription retinoid marketed as a 0.05% gel or cream. It is less ef-
fective than tretinoin against the effects of photoaging, but seems to be less irritating.
Tazarotene
Tazarotene has been shown to reduce wrinkling and fine lines, skin roughness, and
epidermal atrophy. It is a prescription retinoid available as a cream or gel at con-
centrations of 0.05% and 0.1%. Tazarotene has an irritation potential comparable
to that of tretinoin.
Adapalene
Adapalene is approved for the treatment of acne and has been shown to be effica-
cious in the treatment of photoaging. Adapalene has been demonstrated to be less
irritating than tretinoin and is a good choice of a prescription retinoid for patients
with dry and sensitive skin. Adapalene is a prescription retinoid and available in
cream and gel formulations of 0.1% and 0.3% concentration.
When patients are started on topical retinoids, it would seem reasonable to begin
with an over-the-counter retinoid (retinaldehyde, retinol), because they are typically
less irritating. This is especially important for patients with sensitive and dry skin.
After 1 or 2 weeks with an over-the-counter agent, and assuming no skin irritation
is noted, changing to a prescription retinoid would be a logical approach.
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Although treatment with prescription retinoids should build up slowly, some pa-
tients, especially those with dry, sensitive skin, are at considerable risk of develop-
ing irritation and retinoid dermatitis. These symptoms seem to be related to the dose
and type of retinoid used and typically occur about the second to fourth day after
initiating application of a topical retinoid. There will even be a subset of patients
who because of recurring irritation will not be able to apply a prescription retinoid
every day. For these difficult patients, adapalene may be the preferred prescription
retinoid, since it is much less irritating. On the other hand, patients with resistant
and oily skin will be able to use tretinoin in its highest concentration right from the
start, without developing any irritation.
Studies have shown that after 6 to 9 months, the frequency of topical retinoid ap-
plication can be reduced to three times a week without compromising its efficacy.
Topical retinoids can also be used on a continuous basis, because there seems to be
no limit to the length of time a retinoid can be used.
Topical retinoids appear to be an effective long-term antiaging therapy. In general,
the first clinical improvement, often seen after only 1 month of treatment, is an im-
proved smoothness of the skin. After 2 to 4 months of treatment, a lightening of
lentigines and mottled hyperpigmentation can be observed. Finally, coarse skin and
fine lines are usually improved after 4 months of therapy.
Antioxidants
Although the human body possesses endogenous antioxidants, and certain vegeta-
bles and other foods are rich in antioxidants, it is thought that higher levels can be
achieved by supplementation. Consequently, the use of antioxidants as oral supple-
ments or topical formulations may lessen the harmful adverse effects induced by free
radicals. It is believed that a combination of various antioxidants, orally and topi-
cally, may result in sustained antioxidant capacity as a result of synergistic actions
of the combined antioxidants. The biologic effects of antioxidants are summarized
in the box.
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Biologic Effects of Antioxidants
 Antioxidative
 Anticarcinogenic
 Antiinflammatory
 Depigmenting
 Photoprotective

Topical antioxidants are currently marketed for the prevention UV-induced skin
damage and aging, as well as the treatment of rhytids and facial erythema. Based on
current scientific data on antioxidants, the claim that antioxidants may prevent wrin-
kles may be justified. However, there are scant data on the use of topical antioxi-
dants for the treatment of existing wrinkles. The box lists the current most popular
antioxidants included in skin care formulations.
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Depigmenting Agents
Patients with photoaged skin often complain about hyperpigmented lesions, such as
ephilides, lentigines, and melasma or PIH. A number of products are touted as “light-
ening creams.” None of them can magically erase such pigmentary lesions; all re-
quire months of use for visible improvement. Even with prescription lightening prod-
ucts, success is limited. To enhance efficacy it is best to combine the various available
products and procedures that aid in lightening the skin. Optimal treatment requires
the combined use of depigmenting agents, retinoids, sunscreens, and regular chem-
ical peels and light- or laser-based procedures.
Topical depigmenting or skin-lightening agents can be divided according to their
mechanism of action into tyrosinase inhibitors, melanosome-transfer inhibitors,
melanocyte-cytotoxic agents, retinoids, and peeling agents.
Tyrosinase Inhibitors
Hydroquinone is an effective tyrosinase inhibitor that is available in over-the-counter
products in a 2% concentration or less, or as prescription drug in a 3% to 4% con-
centration. Hydroquinone can be concentrated even higher in custom pharmacy for-
mulations. However, higher concentrations are more irritating, leading to side effects
such as skin redness. As with most skin-lightening agents, a prolonged application
of 6 weeks or more is necessary before any improvement becomes noticeable. There
Agents With Antioxidant Activity
 Coenzyme Q10
 Coffeeberry and
Coffea arabica
 Ferulic acid
 Feverfew
 Genistein
 Grape seed extract
 Green tea
 Idebenone
 Lycopene
 Mushrooms
 Pomegranate
 Resveratrol
 Rosemary
 Silymarin
 Turmeric/curcumin
 Vitamin C
 Vitamin E

have been many concerns about the safety of hydroquinone, and in Europe it was
banned in 2000 for general cosmetic purposes. Currently there is an ongoing debate
in the United States as to whether the FDA will ban hydroquinone in over-the-counter
formulations.
Other effective tyrosinase inhibitors found in cosmetic products or prescription drugs
are aloesin and arbutin. Many flavonoids, found in various plants or flowers, dis-
play depigmenting effects, such as resveratrol, gentisic acid, ellagic acid, kojic acid,
hydroxycoumarins, licorice extract, paper mulberry or mulberry extract, and embli-
canin. Most of these products are included in cosmeceuticals.
Melanosome-Transfer Inhibitors
Niacinamide, or nicotinamide, is a popular depigmenting agent with additional an-
tiinflammatory, antioxidant, and immunomodulant properties. Two proteins ex-
tracted from soymilk, namely soybean trypsin inhibitor and the Bowmann-Birk in-
hibitor, have been shown to induce skin depigmentation. Because melanosome
transfer inhibition is reversible, the safety profile of these products is excellent, with
virtually no side effects.
Melanocyte-Cytotoxic Agents
Azelaic acid has been shown to be effective in the treatment postinflammatory pig-
ment alteration.
Antioxidants
Many of the previously discussed antioxidants may lighten cutaneous hyperpigmen-
tation in addition to their photoprotective, anticarcinogenic, and antiinflammatory
activities. Examples of such antioxidants are vitamin C, vitamin E, pycnogenol, and
silymarin.
Other Agents
Alpha-hydroxy acids and beta-hydroxy acid peels can be integrated into a skin care
regimen aimed at the reduction of pigmentary lesions. As they are very safe, people
with virtually any skin type can be candidates for alpha-hydroxy and beta-hydroxy
acid peels.
Retinoids
The effects of retinoids on pigmentation have not yet been fully identified; they seem
to involve various mechanisms. It appears that retinoids directly influence melanocytes
and modulate melanogenesis. Clearly, by an acceleration of the cell turnover of epi-
dermal keratinocytes, topical retinoids promote a decrease in melanosome transfer
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Part III  Nonsurgical Cosmetic Treatments

289
Chapter 10  Skin Care and Dermatologic Treatments
to the keratinocytes and induce dispersion of keratinocyte pigment granules, lead-
ing to uniform distribution of melanin content in the epidermis. An increased epi-
dermal turnover further reduces the cohesiveness of keratinocytes and induces their
desquamation to an accelerated loss of melanin in the stratum corneum. Indirectly,
the retinoid-induced changes in the stratum corneum facilitate the penetration of
other depigmenting agents into the epidermis and increase their bioavailability and
effects. The most popular depigmenting agents included in skin care formulations
are listed in the box.
Antiinflammatory Agents
Patients who complain about sensitive skin with manifestations of erythema, flaking,
tenderness, stinging and/or burning will profit from the inclusion of antiinflammatory
agents into their skin care regimen. Most over-the-counter antiinflammatory agents
are botanicals, some of which were used for centuries in ancient medicines. The box
summarizes the most popular antiinflammatory agents included in cosmeceuticals.
Agents With Depigmenting Activity
 Aloesin
 Arbutin/deoxyarbutin
 Azelaic acid
 Ellagic acid
 Glabridin
 Green tea
 Kojic acid
 Linoleic acid/alpha-
linolenic acid/oleic acid
 N-Acetylglucosamine
 Niacinamide
 Proanthocyanidins
(pine tree and grape
seed extract)
 Rucinol
 Soy proteins (soybean tryp-
sin inhibitor, Bowmann-
Birk inhibitor)
 Vitamin C
 Vitamin E
Agents With Antiinflammatory Activity
 Caffeine
 Chamomile
 Cucumber extract
 Feverfew
 Green tea
 Licochalcone
 Licorice extract
 Mushrooms
 Oatmeal
 Polypodium leucotomos
 Resveratrol
 Silymarin
 Turmeric/curcumin
 Vitamin C

Concluding Thoughts
Skin care is a multibillion dollar market, yet scientific data to support the biologic
effects of various compounds and products are mostly lacking, or studies have not
been designed in a satisfactory way. The only two scientifically well-researched top-
ical cosmeceutical substances are retinoids and sunscreens. Sunscreens protect the
skin from the detrimental influences of UV radiation. Sunscreens reduce photoag-
ing and the development of skin cancer. Retinoids also prevent and partly reverse
photoaging. In addition to the daily cleansing and moisturizing of the skin in accor-
dance with one’s personal needs, retinoids and sunscreens are the two most impor-
tant substances to include in a daily antiaging skin care regimen. The use of antiox-
idants, depigmenting agents, and antiinflammatory agents is based on a sound
rationale. However, most of these products provide only supporting in vitro data.
New ingredients enter the cosmetic market constantly. Unfortunately, clinical data
are scarce or lacking for almost all of these products. Nevertheless, topical products
are an important part of an effective skin care regimen.
Clinical Caveats
 A patient’s skin type and needs should be assessed first.
 Skin care recommendations should be formulated according to the patient’s skin type.
 Every cosmetic patient should be educated on the importance of using sunscreen.
 Patients need instruction on how to use topical retinoids to avoid irritation.
 Light formulations such as lotions or gels should be used for patients with oily skin.
 Richer formulations such as creams can be used for patients with dry skin.
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Draelos ZD, ed. Procedures in Cosmetic Dermatology Series: Cosmeceuticals with DVD.
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A book dedicated to cosmeceuticals that explains in detail various compounds and their
use in dermatology.
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Baumann L. The Skin Type Solution. New York: Bantam Dell, 2006.
This book explains the various skin types defined by Baumann and suggests various skin
care regimens for each of them.
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Bogdan Allemann I, Baumann L. Antioxidants. In Baumann L, ed. Cosmetic Dermatology,
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35:147-156, 1984.
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Kligman AM. The growing importance of topical retinoids in clinical dermatology: a retro-
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Dermatol 15(4 Pt 2):836-859, 1986.
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Botulinum Toxin Injections
for Facial Rejuvenation

ALAN MATARASSO, DAVID SHAFER
CHAPTER 11

296
Part III  Nonsurgical Cosmetic Treatments
S
ince its initial FDA approval in 2002 for the temporary treatment of glabellar
lines, Botox Cosmetic has transformed aesthetic medicine. Indeed, the word
Botox has entered the vernacular, similar to such icons as Xerox for photocopies
and Kleenex for tissues. ASAPS reported that Botox injections continue to outpace the
top five plastic surgery procedures combined. With the FDA approval of Dysport
(BoNTA-ABO, Medicis Aesthetics, Scottsdale, AZ) in 2009, a second botulinum
toxin is now widely available commercially. A comprehensive understanding of the
distinct differences and similarities between Botox Cosmetic (BoNTA-ONA, Allergan,
Irvine, CA) and a non–type A botulinum toxin derivative such as Myobloc (BoNTB,
Solstice Neurosciences, San Francisco, CA) is essential. The primary aesthetic use of
botulinum toxin remains in the face and neck, although novel uses are expanding
daily for aesthetic and nonaesthetic indications.
The aging face undergoes characteristic physiologic and structural changes that are
reflected in the soft tissue layers and skeletal structures. Each region of the face—
forehead, periorbital area, midface, lower face, mouth, and neck—ages in a distinct
manner. Ultimately it is the contrast between what was and what is that motivates
individuals to seek treatment to address this process. Numerous surgical and non-
surgical methods are available to rejuvenate the aging face. The goal of surgery is to
address soft tissue laxity, loss of facial volume, and any tissue hypertrophy. Nonsur-
gical rejuvenation procedures are directed at the texture and quality of the skin and
volume deficiencies in the dermis and underlying soft tissue. Botulinum toxin treat-
ments address rhytids caused by hyperdynamic muscles of animation and, to some
degree, help restore the imbalance created by age. Achieving a balance between dy-
namic rhytids from hyperactive muscles while maintaining natural facial animation
is an important goal of botulinum toxin treatment. Naturally, there will be an over-
lap in the rejuvenation effects of various surgical and nonsurgical treatments. Rhytids
caused by extrinsic aging (photodamage and heliodermatitis) and intrinsic chrono-
logic aging and weight loss are common reasons that patients seek nonsurgical re-
juvenation. Dermal photoaging, which is caused primarily by actinic damage to the
skin, causes dermal thinning at a rate of approximately 6% per decade with thick-
ened, degraded elastic fibers (elastosis), increased ground substance, and reduction
in type I collagen. Concomitant changes occur in the epidermis and the subcu tane -
ous adipose tissue. Muscular animation causes facial lines of aging to appear in most
people and imprints individual patterns of facial expression. This accounts for the
variations in appearance of individuals despite similar muscles of facial animation.
Nonsurgical treatment of facial aging can be described from various perspectives by
the nature of the deformity (wrinkles, folds, and furrows), by the skin layer in which
the defect occurs (epidermis or dermis), or by the technique used to address it (ex-
foliation, dermal and subcutaneous fillers, resurfacing, and chemodenervation). Be-
cause of the many causes of rhytids, various anatomic locations, individual patient
preferences, and the effects of aging, optimal treatment often requires a multifaceted
approach. Consequently, treatment objectives should be to prevent, restore, or re-
verse the cause of the problem. Ultimately the ideal treatment should be individual-

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Chapter 11  Botulinum Toxin Injections for Facial Rejuvenation
ized according to the causes and the patient’s underlying anatomy, and this should
be reconciled with the patient’s goals and tolerance for the therapeutic options.
Nonsurgical Skin Rejuvenation for Facial Rhytids
Office-based nonsurgical skin rejuvenation for addressing facial aging is performed
using one of these three methods, depending on the nature and location of concern:
1. Botulinum toxin is used for chemodenervation of the underlying muscles to
prevent dynamic wrinkles in the overlying skin. In its absence, repetitive mo-
tion of the skin results in rhytids and dermal atrophy. Paralysis of the under-
lying muscle by botulinum toxin prevents continued movement and stress on
the skin, improving the appearance of dynamic lines. Treatment can also im-
prove static lines as dermal repair occurs. Botulinum toxin treatment also
contributes, to some degree, to facial reshaping by decreasing muscle bulk or
altering the dynamic balance between elevator and depressor muscles.
2. Lasers, intense pulsed light (IPL), photorejuvenation, chemical peels, or derm -
abrasion are used for softening static lines and the quality of the skin. These
resurfacing techniques have their greatest benefit in leveling the epidermis
and improving collagen in the dermis. Unlike botulinum toxin treatment,
these resurfacing methods require varying lengths of recovery as the dermis
and epidermis heal. Fractional techniques or subdermal techniques can effec-
tively accelerate recovery time.
3. Tissue fillers are used to replace missing dermal components or subcutaneous
volume. These injectable materials effectively augment areas of dermal atro-
phy by supporting the dermal matrix or by enhancing volume. Fillers show
an immediate effect, and a plethora of products and applications exist.
Nonsurgical methods are often performed together, depending on the desired goal.
These can also be used in conjunction with surgical procedures to complement, en-
hance, or address a condition that cannot be corrected through surgery. Nonsurgical
procedures have broadened the scope of populations and problems that can benefit
from them, but they should not be considered a replacement for surgical rejuvenation
procedures. Self-applied prescription and cosmeceutical topical agents can also be
beneficial and are designed to complement and supplement nonsurgical, physician-
administered, in-office facial rejuvenation.
Of the three broad categories of treatments for nonsurgical facial rejuvenation,
Clostridium botulinum toxin type A (BoNTA-ONA and BoNTA-ABO) injection is
the method that most directly affects the underlying cause of the problem. In this
chapter we will discuss the role of botulinum toxin in the nonsurgical management
of facial aging, its advantages and disadvantages, and clinical applications for pa-
tients undergoing aesthetic surgery.

Dysport was approved by the FDA in 2009 for the treatment of glabellar lines and
joins Botox Cosmetic as the second botulinum toxin type A approved in the United
States for aesthetic treatment. The goals of and results from Dysport (BoNTA-ABO)
treatments are similar to those of Botox Cosmetic (BoNTA-ONA). Nevertheless, it
is essential that injectors understand the differences in unit dosing and dilution tech-
niques between Botox Cosmetic and Dysport to achieve reproducible results with
these two botulinum toxins. We will discuss general reconstitution of Botox Cos-
metic and Dysport, dosing and storage guidelines, injection techniques, posttreat-
ment protocols, and potential complications and how to avoid them.
On the horizon is an additional injectable neurotoxin (RT002) made by Revance Ther-
apeutics (Newark, CA) and jointly licensed with Medicis. RT002 is an investigational
injectable purified botulinum toxin type A that integrates Revance’s patented TransMTS
peptide technology. The goal is that this injectable may enhance delivery of the toxin to
the target site, which may enhance duration and safety of the drug. Also, Revance re-
cently completed a different U.S. phase 2b trial with RT001, a topical botulinum toxin
type A gel for the treatment of lateral canthal lines (crow’s-feet wrinkles).
Evolution of Technique
Botulinum toxin has a long history of use in clinical medicine and has been helpful
for treating a range of conditions for which the principal therapeutic aim is to re-
duce undesired or excessive contraction of striated or smooth muscles. Scott is cred-
ited with the earliest successful use of botulinum toxin in ophthalmology. Thereafter
it was used for the treatment of neuromuscular conditions, and indeed, it is consid-
ered by many clinicians to be a first-line therapy for focal dystonias. Novel uses are
continually developed throughout the spectrum of medical specialties. The box iden-
tifies some of the myriad functional and aesthetic applications for botulinum toxin;
other potential uses of botulinum toxin in medicine are yet to be determined.
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Part III  Nonsurgical Cosmetic Treatments
Partial List of the Uses of Botulinum Toxin in Medical Therapy
Achalasia
Anal fissure
Back pain
Benign prostatic hyper-
trophy
Blepharospasm
Breast reconstruction
and augmentation
Cerebral palsy
Cervical dystonia
Dental procedures
Esophageal stricture
Essential tremor
Facial nerve disorders
Facial spasms
Following Mohs micro-
surgery repair
Gustatory sweating
(Frey’s syndrome)
Headaches
Hyperhidrosis
Inner ear disorders
Masseteric muscle hyper-
trophy
Neck pain
Overactive bladder
Parotid fistulas
Poststroke limb spasticity
Pressure ulcers
Reduced appetite
Spinal cord injury
Strabismus
Teeth grinding
Tourette’s syndrome
Vasospastic disorders
Vocal cord disorders
Temporomandibular joint
dysfunction
Wound healing

Nonaesthetic Uses for Botulinum Toxin Treatment
In 1989 Clark and Berris used botulinum toxin to temporarily restore forehead sym-
metry after a temporal branch motor nerve injury from a face lift. Carruthers and
Carruthers, among others, spearheaded the transition in the use of Botox from oph-
thalmologic to dermatologic and cosmetic applications. They serendipitously ob-
served the effacement of rhytids in patients treated with Botox who had bleph -
arospasm associated with dystonia. Throughout the 1990s, numerous practitioners
reported success with botulinum toxin for eradication of rhytids in an expanding
number of facial regions. By the turn of this century, botulinum toxin injections had
become the most frequently performed nonsurgical aesthetic procedure, and as the
goals of treatment became more sophisticated, its use was expanded to include the
entire face and neck and as a treatment for subtly altering facial shape. If the suc-
cess of a new technology can be measured by its growth and broadening scope of
application, then medical and aesthetic uses of botulinum toxin injections represent
a phenomenon that is rarely seen more than once in a generation.
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Chapter 11  Botulinum Toxin Injections for Facial Rejuvenation
Chronology of Clostridium Botulinum Toxin in Clinical Medicine
Date
Event
Author
1897
Clostridium botulinum neurotoxin isolated
E. Ermengem
1920
Purification attempts
H. Sommer
1946
Crystallized type A purified
E.J. Schantz
1950
Therapy of hyperfunctional muscles
V. Brooks
1973
Pharmacologic weakening of extraocular muscles in monkeys
A.B. Scott
1979
Crystalline botulinum toxin A; batch 79-11
E.J. Schantz
1980
Botulinum toxin for treatment of strabismus in humans
A.B. Scott
1985
Botulinum A exotoxin used to treat blepharospasm
A.B. Scott
1985
Botulinum toxin used to treat spasmodic torticollis
J.K. Tsui
1989
FDA approves Botox Cosmetic for treatment of strabismus,
benign essential blepharospasm, and hemifacial spasm
1990
Botulinum toxin used to treat dystonias
J. Jankovic
1992
Botulinum A exotoxin used to treat glabellar frown lines
J.D. Carruthers,
A. Carruthers
1993
Botulinum toxin used to treat hyperfunction of facial expression
A. Blitzer, M.F. Brin
1997
New lot of Botox reformulated and produced from bulk toxin
2000
Myobloc (BoNTB) botulinum toxin type B approved for treatment
of cervical dystonia
2002
FDA approves BoNT-ONA (Botox Cosmetic) for treatment of
glabellar lines
2004
FDA approves botulinum toxin for treatment of primary axillary
hyperhidrosis
2007
Botulinum toxin injections are the most common aesthetic proce-
dure in the United States, as reported by the American Society
for Aesthetic Plastic Surgery
2009
FDA approves BoNT-ABO (Dysport) for treatment of cervical
dystonia and glabellar lines

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Part III  Nonsurgical Cosmetic Treatments
Role of Botulinum Toxin in Nonsurgical Rejuvenation
Botulinum type A is a powerful neurotoxic agent that specifically and physiologi-
cally denervates the mimetic muscles of facial expression, thereby eliminating their
pull on the overlying skin. The resultant effect is temporary reduction in the appear-
ance of dynamic lines of facial expression and, over time, improvement in static lines
as well. Botulinum toxin therapy has also evolved from just a “wrinkle treatment”
to a method of facial reshaping (elevating soft tissue), because muscular activity causes
rhytids and soft tissue malposition. Drooping soft tissue can be manipulated by
chemodenervation of muscles in the medial brow, lateral brow, corner of the mouth
and jowl by altering the balance between agonist and antagonist muscles. Achiev-
ing an aesthetic balance in the muscles of facial expression while reducing the over-
lying dynamic rhytids is the goal of treatment. For example, the lateral brow has a
propensity for ptosis from chronic animation, because of the lateral extent of the
frontalis muscle, which ends at the temporal crest line, and the depressor effects of
the lateral orbital orbicularis oculi muscle. Consequently, selective treatment of the
medial frontalis muscle and corrugators (depressor) and denervation of the orbicu-
laris oculi (accessory brow depressor) provide lateral brow elevation with a con-
comitant reduction in the appearance of crow’s-feet, resulting in a “chemical brow
lift.” Botulinum toxin can also be used in conjunction with other methods of non-
surgical facial rejuvenation and/or surgery to achieve a variety of aesthetic goals.
There are eight types of serologically active paralytic botulinum toxins; type A (Botox
Cosmetic, Dysport) and type B (Myobloc) are the two agents used in clinical practice.
They exert their action by preventing the release of acetylcholine at the neuromuscu-
lar junction, thereby inhibiting repetitive muscle activity. This leads to the release of
the superimposed cutaneous rhytid, which causes the formation of mimetic wrinkles
or dynamic lines of facial expression and eventually contributing to dermal atrophy
below the wrinkle. Units of biologic activity for different serotypes or formulations
are not equivalent and cannot be easily converted to units of other botulinum tox-
ins despite comparisons that have been suggested because of unresolved informa-
tion. Although all botulinum toxins have comparable effects, no adequate studies
are available for other serotypes such as botulinum toxin type B; thus valid conclu-
sions about the efficacy, dosing, and suggested indications are currently incomplete.
Currently treatment of glabellar frown lines (Botox Cosmetic 2002 and Dysport
2009) is the only FDA-approved cosmetic use of botulinum toxin, and even between
these two type A botulinum toxins, it cannot be overemphasized that despite simi-
lar treatment outcomes, the dilutions and doses are not equivalent. In August 2004
Botox Cosmetic was approved for the treatment of hyperhidrosis. All other cosmetic
uses for botulinum toxin A and B are considered off-label.

Many facial changes associated with the aging face can be attributed to underlying
muscular activity, muscle hypertrophy, and patterns of facial expression for which
botulinum toxin is an appropriate method of treatment. The early focus of botu-
linum toxin therapy was on hyperdynamic upper facial lines. Now its use has been
extended to the midface and neck, often referred to as “extended uses.” In these lo-
cations, unlike the upper third of the face, the goal is often to weaken but not com-
pletely paralyze the muscle to avoid functional loss; for example, softening of verti-
cal “lipstick bleed” lines by weakening the orbicularis oris or the levator labii superioris
alaeque nasi to reduce the upper nasolabial crease. It is also now recognized that re-
laxation of or altering the balance between agonist and antagonist muscles of facial
expression can lead to improvement in soft tissue ptosis and muscle hypertrophy.
An expanded use of botulinum toxin in aesthetic practices extends beyond the upper
face. Nonsurgical reshaping of the lower face can be achieved through injection in
the masseter muscles. This is most commonly done in Asian patients. In this indica-
tion, the goal is not paralysis, but rather temporary muscle atrophy. The depressor
anguli oris or SMAS can also be treated to elevate the corner of the mouth or jowl.
Advantages and Disadvantages
In many respects botulinum toxin injection represents the ideal nonsurgical aesthetic
procedure. It can be safely and rapidly administered, its effects are profound (essen-
tially 100% successful), it is relatively painless, with no patient down time, it is techni-
cally straightforward to use, its effects are reversible within an acceptable period, and
complications are uncommon and self-limiting. Botulinum toxin appears to be one
of those rare therapeutic advances seen periodically over the course of a physician’s ca-
reer that meets, fulfills, and even exceeds its potential and is destined to have a long-
term, sustained impact on the practice of medicine, particularly cosmetic medicine.
Some characteristics of botulinum toxin might also be considered disadvantages,
such as its reversibility or somewhat short length of therapeutic benefit. The toxin
gradually “wears off” 2 to 4 months after treatment. Although some consider this
acceptable, others think that its relatively brief duration is a disadvantage. The cost
of the toxin is a drawback that can serve as an impetus for overdilution to obtain
more volume. In addition, the prolonged consequences, if any, of acetylcholine
blocked by botulinum toxin are unknown. Some concern has been raised in the me-
dia about migration of the neurotoxin into distant sites, including the brain. How-
ever, there have been no reported major adverse consequences from the injection of
botulinum toxin for aesthetic indications using aesthetic dosages.
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Chapter 11  Botulinum Toxin Injections for Facial Rejuvenation

Indications and Contraindications
Certain patient characteristics and anatomic features help to define good, or con-
versely, less acceptable candidates for botulinum toxin injections. The ideal candi-
date should:
 Have a good understanding of the cause of his or her “disagreeable biologic
condition” and the potential role of botulinum toxin in improving it
 Be aware that botulinum toxin’s mechanism of action is to address hyperki-
netic muscles of facial expression, causing them to relax and therefore releas-
ing the overlying wrinkle rather than filling it in or sanding it down
 Have relatively isolated defects that are not necessarily the result of overlapping
conditions (dermal or subcutaneous fat atrophy, excess skin), in addition to
the rhytid
 Understand the chronology of botulinum toxin’s onset of action and need for
continued dosing to maintain the effects, although there is some “retraining” of
muscles with repeated botulinum toxin use, resulting in instrinsic improvement
 Recognize the value of different surgical and nonsurgical treatments and their
various timelines of effectiveness (for example, fillers, 6 months or more, ver-
sus botulinum toxin, 3 months)
Botulinum toxin should be used cautiously in patients with a propensity to bleed
excessively (those with thrombocytopenia; a bleeding disorder such as hemophilia;
or patients receiving anticoagulation therapy such as warfarin [Coumadin], clopid -
ogrel [Plavix], or aspirin). Studies are lacking and there is an insufficient number of
treated patients 65 years of age or older to make valid statements about the efficacy
and safety of botulinum toxin in the elderly. Because of the greater frequency of co-
morbid medical conditions in this population, therapy should be initiated with low
initial doses within the recommended dosage range. Despite any evidence of adverse
effects, botulinum toxin should not be used in pregnant or lactating women or in
women who are attempting to get pregnant. Currently the safety and efficacy of bot-
ulinum toxin have not been established in the pediatric and adolescent populations.
Finally, careful patient selection and counseling are important, because patients who
are ill prepared for the paralytic effect and changes in facial morphology can expe-
rience untoward psychological adjustment following treatment. As with any aes-
thetic procedure, pretreatment photodocumentation is recommended to help resolve
any issues raised by the patient following treatment.
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Common Facial Aesthetic Applications of Botulinum Toxin
 Upper third of the face (frontalis, corrugator supercilii/procerus, orbicularis oculi
muscles)
 Middle third of the face (levator labii superioris alaeque nasi, nasalis muscles)
 Lower third of the face and neck (orbicularis oris, masseter, mentalis, depressor
anguli oris, platysma muscles)
 Following surgery (such as residual corrugator activity after excision), after lipo-
suction of neck or submentoplasty with platysma muscle bowstringing or resid-
ual banding
 Abnormal muscular hypertrophy (such as the temporalis or masseter muscles)
 Combined with other rejuvenating procedures (injectables/fillers, in conjunction
with resurfacing and soft tissue augmentation)
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Chapter 11  Botulinum Toxin Injections for Facial Rejuvenation
Contraindications to Botulinum Toxin Treatment
 Patients with hypersensitivity to the ingredients (albumin, sodium chloride, botulinum
toxin)
 Patients with neuromuscular disease (myasthenia gravis, Easton-Lambert syndrome,
motor neuron disease)*
 Patients treated with botulinum toxin concurrent with other drugs that interfere with
neuromuscular transmission—antibiotics (certain aminoglycosides, lincosamides, poly -
myxins), penicillamine, quinine, calcium channel blockers, neuromuscular-blocking
agents (atracurium, succinylcholine), anticholinesterases, magnesium sulfate, and
quinidine—all of which may increase the paralytic effect of the toxin (also potentially
other serologic types of botulinum)*
 Pregnant or lactating women
 Patients receiving anticoagulation therapy/aspirin (a relative contraindication)
 Patients with inappropriate anatomy (skin laxity, photodamage)
 Patients with poor psychological adjustment or unrealistic expectations
 Patients who are allergic to cow’s milk protein (BoNTA-ABO: Dysport)
*These contraindications are based on interactions with drugs and intrinsic muscle disease, which could prolong the
neuromuscular blockade effect of botulinum toxin.

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Part III  Nonsurgical Cosmetic Treatments
Pertinent Anatomy
This illustration of relevant facial muscular anatomy shows the most common of
the 44 facial muscles in which botulinum toxin is injected. The use of botulinum
toxin for rhytids or to reshape or reposition structures requires an in-depth under-
standing of the function and location of the muscles of the face, their interactions
(agonist versus antagonist), and the unique anatomic features of each region of the
face. It is essential to precisely locate the muscles that are to be treated either clini-
cally or by means of electromyography (EMG). We prefer to have the patient acti-
vate the muscle to be treated by a forced, exaggerated contractile motion intended
to mimic the action of the muscle. The surface topography of that muscle will then
be evident by the rhytid that is perpendicular to the body of the muscle (for instance,
the orbicularis oculi) or enlargement of the muscle (for instance, the platysma).
Anatomic landmarks, danger zones, or areas of altered anatomy from previous sur-
geries should be identified, along with the specific dosages appropriate to common
muscle sites of botulinum toxin injection.
Orbicularis oculi muscle
Orbital portion
Tarsal portion
Zygomaticus
minor muscle
Zygomaticus
major muscle
Depressor anguli
oris muscle
Platysma muscle
Frontalis muscle
Procerus muscle
Corrugator supercilii
muscle
Levator labii superioris
alaeque nasi muscle
Levator labii
superioris muscle
Nasalis muscle
Orbicularis oris muscle
Mentalis muscle

Botulinum Toxin: General Dosing Guidelines*
Area
Botox Cosmetic
Dysport
(corresponding
(BoNTA-ONA)
(BoNTA-ABO)
rhytid)
Muscle
Units
Units
Anatomic Landmarks or Danger Zones†
Forehead (hori-
zontal fore-
head lines)
Glabellar com-
plex (vertical
and transverse
glabellar lines)
Bunny lines
(side of nose)
Crow’s-feet
(lateral can-
thal rhytids)
Upper third of
nasolabial
fold
Upper lips (ver-
tical rhytids)
Marionette
groove
Chin (cobble-
stoning)
Neck (vertical
bands)
Masseter hyper-
trophy (infero-
lateral facial
fullness)
Frontalis
Corrugator super-
cilii/pro cerus/
orbicularis oculi
(medial fibers),
depressor super-
cilii
Nasalis (transverse
portion)
Orbicularis oculi
(lateral fibers)
Levator labii
superioris
Orbicularis oris
Depressor anguli
oris
Mentalis
Platysma
Masseter
30-60
50-80
6-15 (per side)
20-60 (per side)
5-7
4-24
20 (per side)
10-20
40-80 (per
band)
100-300 (per
side)
Inject in gridlike pattern; lateral por tion of
frontalis for 1-2 cm above brow injection
will result in inability to raise eyebrow, or
“brow ptosis.” To avoid this, inject above
lowest fold produced by muscle action
and M point. This will cause wrinkle to
remain, maintaining brow elevation.
Inject in V pattern, staying medial to mid -
pupillary line and avoiding injection below
0.5 cm from medial edge of eye brow.
Inject just transverse portion of nasalis
muscle.
Stay 1 fingerbreadth lateral to orbital rim and
3-4 injections in fan-shaped pattern. Avoid
injection too far inferior (to zygomaticus
major mus cle) and possibly elevate cheek
to demon strate lines caused by zygomati -
cus muscle as opposed to pure orbicularis
oculi muscle (squint).
Confine injection to region of piriform
aperture between nasolabial fold and
nasal ala.
Inject small aliquots in lower third (for upper
lip) and upper third (for lower lip) of
orbicularis oris muscle.
Identify muscle with patient ac tively pursing
lips/chin 1 cm lateral and 1 cm inferior to
angle of mouth.
Have patient project lower lip and chin
upward. Inject at 3-5 sites intramus cularly
into “cobblestoned” chin, just inferior to
mental sulcus.
Isolate muscle cords with nondominant hand
and inject en tire length of body of muscle
at 1-1.5 cm intervals from clavicle to its
insertion in mandible. Inject subcutane -
ously for horizontal necklace lines. Avoid
sternocleidomastoid muscle.
Inject 5-6 points into body of muscle at
mandibular angle. The goal is selective
muscle atrophy, not paralysis.
*It cannot be stressed enough that Botox Cosmetic and Dysport do not have equivalent dosing on a unit-per-unit basis and that dosing guidelines for
Dysport have not been firmly established.
†The surgeon must be aware of the effect that surgically altered anatomy has on muscle position. Dosage should be individualized according to muscle
mass, patient response, sex, age, the desired effect, the time interval since the previous exposure, and the condition being treated.
20-60
20-40
2.5 (per side)
5-15 (per side)
2-5 (per side)
3-10
2-5 (per side)
5-10
20-40 (per
band)
25-30 (per
side)

Fundamentals
Pharmacology and Reconstitution
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Botulinum neurotoxin type A (BoNTA-ONA: Botox Cosmetic and BoNTA-ABO:
Dysport) is one of eight serologically distinct and species-specific toxins produced by
the anaerobic bacterium Clostridium botulinum. It is a gram-positive, spore-forming,
obligate anaerobe that is found naturally in the soil. It is produced by fermentation
of strain C. botulinum type A grown in a culture medium.
The culture solution is purified and dissolved in sterile sodium chloride containing
human albumin and is then sterile-filtered before filling and vacuum drying. It is
commercially available as a sterile, lyophilized powder without preservatives. Each
single vial of Botox Cosmetic contains 100 units (10% variation) of botulinum type A
neurotoxin complex, 0.5 mg of human albumin, and 0.9 mg of sodium chloride.
A 50-unit vial of Botox Cosmetic is also available.
Each vial of Dysport contains 300 units of botulinum type A complex, 125 g of
human serum albumin, 2.5 mg of lactose, and trace amounts of cow’s milk protein.
A 500-unit vial of Dysport is also available for cervical dystonia. It is important to
note that Botox Cosmetic and Dysport are not equivalent on a unit-per-unit basis—
100 units of Botox Cosmetic is not equivalent to 100 units of Dysport. Each prod-
uct is kept refrigerated at 2° to 8° C (35.6° to 46.4° F). At the time of use, it is re-
constituted with 0.9% sodium chloride injection, resulting in a clear, colorless,
odorless solution that the manufacturer recommends be used within 24 hours.
The rubber stopper can be removed from the vial before mixing to prevent foam-
ing, which anecdotal reports state can potentially denature the toxin, and the saline
solution is introduced by means of a 1 ml Luer-Lok syringe with a 22- or 25-gauge
needle. The same needle is used to withdraw the reconstituted solution and is then
replaced with a 1⁄2-inch 30- or 32-gauge needle, which is used for injection.

Mechanism of Action
Both BoNTA-ONA (Botox Cosmetic) and BoNTA-ABO (Dysport) are composed of
botulinum toxin type A, each with a unique toxin/protein complex. The different
complexes result in the differences in unit dosing between the two products. Once
injected, the botulinum toxin core quickly dissociates from the complex and diffuses
to its site of action. The toxin produces chemodenervation by preventing release of
acetylcholine at the neuromuscular junction of the peripheral nervous system and
at ganglionic nerve terminals of the autonomic nervous system within 6 to 36 hours
of exposure to muscle with maximum effect up to 7 to 14 days. The neurotoxic ef-
fects of botulinum toxin occur in three phases:
1. Binding
2. Internalization
3. Neuromuscular blockade
Following these phases, a chemical denervation results, with associated clinically
flaccid paralysis of the targeted muscle. At therapeutic doses the toxin induces paral-
ysis limited to the injected muscle; however, the toxin has the potential to cause
paralysis or weakness of adjacent muscles by diffusion and spread. The extent of
muscular paralysis and atrophy correlates directly with the amount of toxin injected
(concentration and volume of toxin solution). Diffusion results from toxin moving
down its concentration gradient, which is affected by local receptor concentration.
The spread depends on the solution volume and injection technique (physically push-
ing the toxin from the area of injection). There is an ongoing turnover (redevelop-
ment) of neuromuscular junctions so that muscular function gradually returns after
approximately 3 months, and axonal sprouting and reorientation of muscle fibers
prevent permanent paralysis of muscles that are treated repeatedly.
Toxicity
Botulinum toxin is one of the most potent and neurospecific toxins known. It is es-
timated that in a 70 kg adult, the lethal dose of crystalline botulinum type A would
be approximately 0.09 to 0.15 mg by the intravenous or intramuscular route, 0.7
to 0.9 mg by inhalation, and 70 mg if ingested orally. Considering the type available
in the United States, it would be inaccurate to consider it as a potential bioterror-
ism agent, because each vial contains only about 0.3% of the estimated human lethal
inhalation dose and 0.005% of the estimated lethal oral dose. The toxin does not
penetrate intact skin, and person-to-person transmission does not occur.
The lethal dose of Botox Cosmetic is measured in units, with 1 unit being the lethal
dose of toxin, causing death in 50% of a group of 18 to 20 g female Swiss Webster
mice within 3 days of intraperitoneal injection. The median lethal dose (LD50) has
been estimated to be 2700 (2500 to 3000 units) in a 70 kg human, based on the me-
dian lethal dose of approximately 40 units/kg in primates. Species-specific sensitiv-
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Chapter 11  Botulinum Toxin Injections for Facial Rejuvenation

ity to the toxin precludes precise calculation of the human LD50. The normal dose
that does not produce toxicity is not known; however, single doses exceeding 500
units of BoNTA-ONA may produce acute symptoms and signs of botulism.
Dosages
The manufacturer’s recommendations and initial FDA approval of Botox Cosmetic
for treatment of the glabellar area were based on 2.5 ml (0.1 ml  4 units) of un-
preserved normal saline solution per 100 units of Botox Cosmetic for reconstitu-
tion. The maximum total recommended dose is 300 to 400 units at any one session
and not more than 400 units over a 3-month period. The maximum dose of Dys-
port is 1000 units over a similar period. The dosage should be altered according to
anatomic location, muscle mass, age, and sex of the patient, the patient’s prior ex-
perience with botulinum toxin, the desired effect, the time interval since the previ-
ous exposure, and the condition being treated. Male patients may have a less pro-
found and long-lasting result with botulinum toxin.
An acute awareness of the differences in dosing between Botox Cosmetic and Dys-
port is essential, since the “units” are not interchangeable. In general, Dysport is less
active on a unit-per-unit comparison with Botox Cosmetic, which means that more
units of Dysport are required to achieve similar clinical effects. With normalized clin-
ical dosing, similar results can be achieved. Some studies, with electromyographic
evidence, show that Dysport may achieve a clinic effect faster and maintain results
longer than Botox Cosmetic. Continued clinical experience is required. Addition-
ally, some practitioners have raised the concern of the smaller complex size of Dys-
port leading to a higher risk of diffusion. However, studies show that the toxin
quickly dissociates from the complex under physiologic conditions once it is injected,
precluding complex size from resulting in differences in diffusion. Perhaps because
of this, some have claimed that Dysport produces a softer, more natural appearance.
A distinction should be made between diffusion and spread. Diffusion is attribut-
able to the total dose and receptor concentration because the toxin moves down its
concentration gradient. Spread, on the other hand, is dependent on the volume in-
jected and the injection technique; injecting a higher volume leads to increased phys-
ical distribution of the product as the fluid is pushed through the tissues from the
point of injection. So diffusion or spread is a function of concentration gradient and
physical force and is not attributable to the specific brand or formulation of toxin.
Dilution and Storage Considerations
There are two areas of frequent controversy regarding botulinum toxin that have yet
to be determined: (1) the appropriate dilution of the toxin and (2) the method and
length of storage of the reconstituted toxin. The manufacturer provides a table of 1
to 10 ml of dilution; however, physician preference remains the deciding factor. The
glabella is the only area for which the FDA has approved injections and that is based
on a dilution of 2.5 ml into a 100-unit vial of Botox Cosmetic or 2.5 ml and 1.5 ml
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Part III  Nonsurgical Cosmetic Treatments

dilutions into a 300-unit vial of Dysport. Large dilutions with lower concentrations
of toxins require larger volumes of injections to achieve the desired result, which
can increase the potential for spread of the toxin to unwanted surrounding areas.
For that reason we prefer a low volume and high concentration of botulinum toxin.
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Chapter 11  Botulinum Toxin Injections for Facial Rejuvenation
Type and Concentration of Botulinum Toxin
Type of Botulinum Toxin
Concentration (units/ml)
Dysport 300-unit vial
1 ml
30/0.1
1.5 ml
20/0.1
2.5 ml
12/0.1
3 ml
10/0.1
Botox Cosmetic 100-unit vial
2 ml
5/0.1
2.5 ml
4/0.1
4 ml
2.5/0.1
Botox Cosmetic 50-unit vial
1 ml
5/0.1
2 ml
2.5/0.1
The length of viability of reconstituted toxin and the method of storage are also sub-
ject to controversy. We prefer using the toxin within 24 hours of reconstitution, dur-
ing which time the unused toxin is kept refrigerated at 2° to 8° C. Some physicians
refrigerate the toxin after reconstitution and have demonstrated a viable, albeit pro-
gressive, loss of drug efficacy over a 30-day period. If the toxin is stored, it should
be reconstituted with bacteriostatic 0.9% sodium chloride preserved with benzyl al-
cohol to avoid bacterial contamination. Once the cap has been removed, the vial
contents are no longer sterile.
Pretreatment Assessment
Physical Examination and Patient Education
A staff member interviews and evaluates the patient, who is given an informational
packet to read before consultation with the physician. The medical history includes
the patient’s prior treatments with botulinum toxin, topical agents, or injectable
fillers. The patient is asked to actively contract the intended muscle to be treated in
front of a hand mirror, which helps to identify the muscle and serves as a tool for
patient education. The patient is instructed to accentuate the specific facial lines to be
treated by frowning (glabellar lines), squinting (lateral canthal lines), or elevating
the brow (horizontal forehead lines). Patients never scrutinize their faces as much

before a procedure as they do after it has been completed; therefore it is important
to identify and point out to patients the naturally occurring asymmetries that are
present before treatment and to possibly obtain photographic documentation of base -
line status. For example, there can be more aging on the left side of the face in gen-
eral, and crow’s-feet in particular, because of exposure to the elements while a per-
son is seated on the driver’s side of an automobile, and this side may need more
toxin. Coexisting conditions in the field of treatment that will not be improved with
injections (such as loose skin in the neck and static lines in the periocular region)
should be identified and discussed with the patient. Planning for concurrent dermal
filler or subsequent surgical treatment can be discussed. Unless one has prior expe-
rience that the patient has significant enough dermal atrophy to require correction
with filler, we prefer to denervate the muscle with botulinum toxin and await the
therapeutic benefit before determining the need for dermal filler supplementation.
Before treatment, the patient should be examined for preexisting ptosis. There are
three types of “ptosis” that can be encountered before or subsequent to treatment:
1. Drug-induced eyelid ptosis results from diffusion of the toxin to the upper
eyelid levator aponeurosis after injection of the corrugator muscle or crow’s-
feet. The cause and effect of this are largely unknown and speculative, since
studies with direction injection of botulinum toxin into the levator muscle
have occasionally failed to achieve ptosis. The treatment is medications that
stimulate Müller’s muscle, such as Naphcon A eyedrops 3 to 4 times daily or
apraclonidine 0.5% after consulting with the patient’s ophthalmologist. These
drops provide approximately 1 to 2 mm of elevation and require continued
use for sustained effect. Patients should have an eye examination before the
agents are used; they should not be administered in patients with glaucoma.
2. Preexisting eyelid ptosis reflects the unmasking of preexisting upper lid pto-
sis that had been compensated for by frontalis muscle activity; treating the
frontalis muscles with botulinum toxin unmasks this. The treatment is care-
ful preoperative identification with administration of Müller’s muscle ago-
nist agents as indicated.
3. True brow ptosis is caused by loss of frontalis muscle activity, which is at-
tributed to injection of the lower border of the lateral frontalis muscle 1 fin-
gerbreadth below or above the brow. Patients may present complaining of
heavy eyelids despite a lack of eyelid ptosis or inability to put on eye shadow.
The correct treatment is to avoid this area and/or inject the antagonist de-
pressor muscles, known as the M point of the orbicularis oculi. Before treat-
ment, the efficacy against all forehead lines and the effect that has on brow
position are discussed with the patient, including not treating the lower fore-
head lines to allow eyebrow movement. This is frequently the area of greatest
patient concern. Moreover, surgical procedures to elevate and stabilize the
lateral brow enable patients to have the lower rhytids treated with botulinum
toxin. In addition, with elevation of the lateral brow there is less stimulus for
the patient to contract the brow upward. Thus even without botulinum toxin
the surgery alone improves the wrinkles.
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Part III  Nonsurgical Cosmetic Treatments

Patients are instructed to cease using the following, if feasible, for 10 to 14 days be-
fore treatment to minimize ecchymosis: aspirin products, compounds containing vi-
tamin E, nonsteroidal antiinflammatory agents, and dietary supplements that pre-
dispose them to bleeding or coagulation problems. As with any medical procedure,
patients are asked to sign an informed consent form and HIPPA forms before treat-
ment. Photographic documentation is beneficial. In addition, it is important to dis-
cuss the benefits and limitations of botulinum toxin treatment and review the alter-
natives or supplemental treatments that are valuable. Patients’ questions are answered
before treatment. We have an in-depth discussion with the patient about specific con-
cerns, the cause of their “disagreeable biologic condition,” and the therapeutic op-
tions available. We explain the specific role of botulinum toxin, the intended results,
the length of its effectiveness, and potential complications. We are also careful to
point out that unlike most filler materials, with which patients see an immediate re-
sult, the response to botulinum toxin is delayed (up to 14 days for final results).
Pretreatment Planning
Patient Preparation
Before treatment and the application of topical anesthesia, all areas of the face are
cleansed of makeup and lipstick. Because patients want maximal benefit with min-
imal adverse effects or complications and a rapid recovery, every effort should be
made to reduce patient discomfort. Therefore a topical analgesic is applied (lido-
caine 4% [LMX4; Ferndale Laboratories, Ferndale, MI]) if requested; the patient is
offered an anxiolytic agent if warranted; and cold compresses are applied to the in-
tended sites to lessen discomfort. With the patient in an upright position, the prod-
uct is injected into the region of the muscle according to its precise anatomic loca-
tion. The dose of botulinum toxin varies, de pending on the factors mentioned.
Injecting a local anesthetic mimics the effect of the botulinum toxin action, which
can serve as an educational tool for the patient.
Markings
For a typical office treatment, surgical markings are unnecessary, because in contrast
to a surgical procedure, the patient is asked to repeatedly contract the muscle to
identify sites for injection. The upright position does not distort the injection area.
If the patient is having botulinum toxin injections intraoperatively, markings are
made over the presumed body of the muscle, not necessarily over the deepest der-
mal rhytid.
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Part III  Nonsurgical Cosmetic Treatments
Technique
With the patient in a seated position and after suitable preparation, each muscle of
concern is identified and isolated. The intended muscle is isolated and stabilized or
grasped with the nondominant hand. Injections are made into the region of the mus-
cle according to its precise anatomic location.
Injection proceeds using proper injection techniques (injecting slowly perpendicu-
lar to a noncontracted muscle). Botox can be injected into various levels, such as the
body of the muscle (corrugator, platysma), deep subcutaneous tissue overlying the
muscle (frontalis), or superficially (orbicularis oculi). A serial puncture technique is
preferred, rather than a bolus that is spread by massaging. Some physicians use EMG
guidance to identify and isolate muscles, but this may have limited benefit in areas
in which muscles are palpable, visible, and easily identified, such as those in the face.
The purported advantage of EMG guidance is that it allows more accurate identifi-
cation of the neural motor endplate, facilitating more precise injection and improv-
GENERALLY RECOMMENDED INJECTION SITES
Forehead
White dots
Frontalis muscle
Black dots
Glabellar complex
Eyelid
Yellow dots
Orbicularis oculi muscle
Red dots
M point of orbicularis oculi
Midface
Green dots
Upper nasolabial fold
Lip
White dots
Vertical lip lines
Chin
Blue dots
Mentalis muscle (cobblestoning)
Neck
Yellow dots
Platysma bands
1
11-1 Botox Cosmetic
and Dysport:
anatomy, supplies,
techniques, and
results

ing the effectiveness of lower doses of botulinum toxin. However, for general aes-
thetic indications this is rarely necessary. A postinjection protocol is then initiated.
The muscles are sequentially injected (intramuscularly [deep], or superficially [sub -
cutaneously]). The solution is withdrawn in aliquots of 2.5 to 5 units of Botox Cos-
metic or 5 to 10 units of Dysport (smaller increments for nasolabial and lip areas)
at intervals of 0.5 to 1.5 cm apart, depending on the muscle and the intended result.
With familiarity, the clinician performing the injections develops a sense of the nec-
essary volume of injectate without observing the volume markings on the syringe.
Some clinicians believe that botulinum toxin has a 3 cm target of spread (not un-
wanted diffusion from movement). Although this may be so, it may vary in differ-
ent regions, and the perimeters of the zone of spread should not be relied on for
chemodenervation; instead, sites beyond 1 to 1.5 cm require their own injection for
reliable paralysis (wider zones of injection are feasible in the frontalis muscle). When
completing each injection, the surgeon withdraws the hub of the syringe slightly by
the thumb to prevent unnecessary spillage of the toxin. Alternatively, an insulin sy-
ringe can be used. These syringes do not have a Luer-Lok, so less toxin will be wasted.
The disadvantages of an insulin-type syringe are that it is difficult to draw the solu-
tion into the syringe with the single-use needle, and the needle dulls quickly.
The fundamental principles for a successful outcome with botulinum toxin include
the following:
 Proper reconstitution and storage of toxin
 Proper patient education, consent, and pretreatment preparation
 Proper muscle identification and isolation, and matching of the toxin dose to
each individual patient’s needs to achieve the intended result
 Proper injection technique
 Proper posttreatment protocol
 Frequent needle changes (the needle dulls with repeated use from multiple in-
jections)
Combination Treatments
Botulinum toxin is commonly injected alone as monotherapy, although combina-
tion treatments during the same or subsequent sessions (fillers and resurfacing) can
be used as necessary to treat the different layers of the skin and various conditions.
For example, botulinum toxin can be injected into the frontalis muscle for dynamic
forehead lines while avoiding the 1 to 2 cm above the brow so that muscle activity
remains; substituting a filler in this area can help ameliorate the residual static lines.
For deep glabellar lines (static and dynamic), a combination of botulinum toxin and
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dermal filler may be necessary to achieve an optimal result. Numerous combinations
are also possible. For example, botulinum toxin may be injected into the orbicularis
oris muscle in conjunction with resurfacing (not simultaneously) or fillers to the lip
and/or to the vertical lip lines. Botulinum toxin can also be used for crow’s-feet, with
laser resurfacing to the lower lid skin and fillers to the lower crow’s-feet to avoid
paralysis of the zygomaticus major muscle. When botulinum toxin is combined with
a filler, it tends to prolong the longevity of the filler by decreasing the metabolism in
the surrounding tissue. Botulinum toxin also has the potential to enhance the effects
of laser resurfacing by improving collagen reorganization while the skin is paralyzed.
In some areas, such as the upper third of the face, the physician can delay injecting
filler material until the botulinum toxin is fully effective before resorting to the use
of a filler. However, with nonsurgical rejuvenations, mixing and matching of products
is common. One must keep in mind the differing timelines for longevity of the prod-
ucts or techniques used. Moreover, botulinum toxin can be used in conjunction with
various depth peels and laser resurfacing.
Posttreatment Care
The most common adverse sequelae, ecchymosis and erythema, can be managed by
applying gentle pressure with or without cold compresses to the treated site imme-
diately after each site is injected. Patients are advised to actively contract the treated
muscle in an attempt to (theoretically) enhance toxin uptake by causing more rapid
internalization of the toxin (however, the usefulness of this technique has not been
proved). Patients are instructed to resume normal activities immediately after their
treatment session but are advised to remain upright and to avoid lifting, bending,
or straining for 3 to 4 hours, particularly when the treated site is in the upper third
of the face, to help prevent unwanted spread of the toxin. Essentially, the patient
should hold his or her head upright as if balancing a book on it. Thereafter all ac-
tivities are unrestricted. The consensus is that flying in an airplane and heat expo-
sure do not have an adverse impact. The application of camouflaging agents or
makeup is unrestricted.
Although adverse sequelae are self-limited, they do occur, and it is best to counsel
the patient reassuringly. For the occasional patient who complains of headaches,
nonaspirin products can be given. Vitamins and nutritional supplements can be ad-
ministered as indicated, although whenever possible it is helpful to avoid these for
10 to 14 days before treatment to help prevent ecchymosis. Patients can return for a
postinjection examination after 2 weeks and within the first 4 to 6 weeks if they sus-
pect a therapeutic failure; beyond that it cannot be ascertained whether the muscle
activity represents normal wearing off of the toxin or a therapeutic failure. Other-
wise, patients are advised to return after a minimum of 3 months for additional treat-
ments if they want to maintain the results.
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Presumed therapeutic failures can often be attributed to the following:
1. A misunderstanding of the intended effect
2. The recruitment of surrounding muscle that was not intended to be affected
3. The patient’s not being informed that residual static lines will not be improved
by botulinum toxin treatments
4. A persistent rhytid resulting from dermal atrophy in the absence of underly-
ing muscle activity
The effects of botulinum toxin injections can be observed as early as a few days later
or up 14 days after treatment, depending on which muscle is treated and a variety
of other factors. It is therefore advisable to wait 14 days, but within 4 to 6 weeks,
and then examine a patient who believes he or she has had an inadequate response.
If there is still residual muscle activity, additional botulinum toxin injections may be
indicated. We usually do not advise “booster injections” within the 3 months after
injection as the toxin is naturally wearing off.
Muscle activity begins to return gradually and waxes and wanes until approximately
3 to 4 months after injection, when full muscle mobility resumes. When proper pre-
cautions are taken to prevent complications of individual procedures, botulinum
toxin can be administered before, during, or after surgical or resurfacing procedures
without any adverse effects attributable to the combined modalities. However, con-
sideration must be given to two situations related to botulinum toxin in a surgical
patient:
1. If botulinum toxin is used intraoperatively or immediately postoperatively,
the patient is potentially less likely to maintain the recommended inactivity
to prevent spread.
2. In a postsurgical patient, the injector should be made aware of any anatomic
(muscle) alterations related to the surgery.
Problems and Complications
Complications fall into three general categories: local, regional, and systemic. In ad-
dition, toxin “deactivation,” immunologic responses, and therapeutic failure can be
considered complications. Normal sequelae that are not true complications but that
the patient may consider complications include needle marks, swelling, bruising, and
mild erythema, or an earlier onset in one anatomic site versus another. Many of these
normal effects that patients may consider abnormal are related to their preconceived
expectations. The time of onset is an important indicator of a complication versus
a normal sequela, because technical reactions are likely to be observed earlier than
true complications.
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Local, Regional, and Systemic Complications
There can be a fine line between what is considered normal sequelae and local com-
plications. Local complications can include injection site pain, swelling, edema, ery-
thema, rash bruising, ecchymosis, tenderness, headache, and short-term hypesthe-
sias and can be related to the injection sites. S.L. Matarasso has summarized
techniques to minimize these local complications.
The most notable and disfiguring regional complications occur when the toxins dif-
fuse or migrate, spreading the neuromuscular blockade to unintended adjacent sites
such as the zygomaticus major, which could be inadvertently injected during treatment
of the orbicularis oculi, creating upper lip asymmetry or dysphagia or neck muscle
weakness from platysma muscle injection. Other regional complications include loss
of facial expression (a masklike countenance) from excessive paralysis, rendering
the patient expressionless, or incomplete muscle paralysis with residual rhytids (sim-
ilar to that which occurs in local complications).
Systemic reactions can include nausea, fatigue, severe generalized muscle weakness
(only reported for patients in whom it was used in larger doses for noncosmetic pur-
poses), malaise, flulike symptoms, distant rashes, respiratory arrest, and death. At
therapeutic doses, botulinum toxin is not expected to be present in peripheral blood
at measurable levels following intramuscular injection, nor does the amount of drug
administered in a typical session appear to induce systemic effects. Distant neuro-
muscular effects have been documented but only from single-fiber EMG studies. The
significance of these findings remains unclear. Isolated nervous system, respiratory,
ocular, gastrointestinal (in patients with cervical dystonia—oral dryness, nausea,
dysphagia, and dyspepsia), musculoskeletal, cardiovascular, dermatologic, and gen-
itourinary complications have been reported with general (noncosmetic) uses of bot-
ulinum toxin and rarely if ever from the dosage range required for cosmetic usage.
In fact, most of the literature on complications is from noncosmetic sources. It is
suggested that practitioners report adverse events with Botox Cosmetic to the Med-
ical Affairs Division of Allergan at 1-800-433-8871 or the FDA at 1-800-FDA-1088.
Immunologic Reactions
Immunologic complications include acute type I reactions and may be attributable to
human serum albumin. This may result from the presence of circulating immunoglob-
ulin G antibodies and is reported to occur in 3% to 5% of patients treated for cer-
vical dystonia where large volumes of toxin are used. Since 1997, with a reduction
in protein content to 20% of the original volume in the solution, there have been
no reports of this complication. The development of antibodies seems to correlate
with an increasing number of injections, frequency of treatment, and total cumula-
tive dose of toxin. Since we began using botulinum toxin for aesthetic indications,
we have encountered only two patients who were resistant to treatment, presum-
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ably because of the neutralizing effect of antibodies. Limiting the total amount of
toxin to less than 300 to 400 units of Botox Cosmetic per session and avoiding
booster injections for a minimum of 3 months are recommended to prevent forma-
tion of these antibodies. Serum analysis can be performed to analyze for circulating
antibodies, but is rarely indicated (PacificBiolabs.com). Injecting 15 units of Botox
Cosmetic into one side of the frontalis muscle to observe for asymmetrical clinical
effect can be used as a simple clinical test for resistance. Botulinum toxin type B
(Myobloc/Neurobloc) may be considered as an alternative in patients with immuno-
logic resistance to botulinum toxin type A as well as for other purposes. It is unlikely
that another botulinum toxin type A (Dysport) would benefit a patient resistant to
another botulinum toxin type A (Botox Cosmetic).
Therapeutic Failures
Therapeutic failures can range from no effect whatsoever after an injection to an
unintended effect. A therapeutic failure can originate at various stages in the treatment
process. Improper mixing (foaming), improper dilution or storage (wrong temper-
ature), incorrect muscle identification, or failure to distinguish a static from a dy-
namic rhytid can also result in a therapeutic failure.
Botox “signs” are considered an unintended result caused by recruitment of un-
treated adjacent muscles, or an abnormal appearance resulting from loss of func-
tion in a treated muscle can be interpreted as a failure.
Outcomes
Results with botulinum toxin as a primary monotherapy or in conjunction with
fillers, resurfacing, or surgery, when injected appropriately, are generally excellent.
Indeed, unlike almost any other surgical or nonsurgical procedure used for facial re-
juvenation, botulinum toxin can provide an “all or none” response (unless weaken-
ing of the muscle is the goal), making it 100% effective.
The most common causes of patient dissatisfaction with botulinum toxin treatment
include the following:
 Inadequate understanding of the role of botulinum toxin in facial rejuvena-
tion.
 Unpreparedness for the effects of botulinum toxin treatment, including tem-
porary paralysis or altered balance of the muscles of facial expression.
 The psychological consequences of altered facial appearance.
 Suspected therapeutic failure that can be attributed to the recruitment of sur-
rounding untreated muscles.
 Short-term local complications.
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 Rare general, systemic, or immunologic complications.
 In the face, the most common concerns occur with treatment of the lateral
third of the frontalis muscle over the brow, where injection will ameliorate
rhytids but will also limit the patient’s ability to elevate the eyebrows.
Results
This 57-year-old woman complained of forehead and glabellar wrinkling and cob-
blestoning of her chin. She underwent Botox Cosmetic injections to her frontalis
(forehead), corrugator, procerus, and mentalis muscles. She is seen 4 weeks after
treatment, with reduction in the appearance of her rhytids and cobblestoning in the
mentalis area.
This 38-year-old woman presented with perioral rhytids and upper facial rhytids.
She underwent botulinum toxin injections to her forehead, glabella, crow’s-feet area,
and her upper lip. She is seen 6 weeks after treatment. The results of her perioral
treatment reveal a reduction in the vertical lip lines. Treatment here must be tem-
pered with an awareness of the potential for loss of function and lip symmetry.

This 46-year-old woman presented with upper facial rhytids and cobblestoning of
her chin and neck cords. She was treated with Botox Cosmetic injections to her
frontalis muscle (forehead), corrugator muscle complex, orbicularis oculi muscles,
and mentalis and platysma muscles. She is seen 1 month after treatment.
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Chapter 11  Botulinum Toxin Injections for Facial Rejuvenation
This 62-year-old woman presented with hypertrophic platysma cords and horizon-
tal necklace lines. She was treated with botulinum toxin injections to her vertical
platysma muscles and horizontal neck creases. She is seen 1 month after treatment.
Improvement is evident in her hypertrophic right neck muscle cord, and the neck-
lace lines have softened.

This 52-year-old woman presented with periocular and glabellar rhytids. She was
treated with Botox Cosmetic injections to her corrugator-procerus muscle complex
and the lateral orbicularis oculi muscle. She is seen following injection at the onset
of the therapeutic benefits. The reshaping in the arch of her lateral brow is evident;
this was produced by deactivating the depressor muscles in this area and allowing
the elevator (frontalis) muscles to act unopposed.
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Continued
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Concluding Thoughts
Botulinum toxin injection is an aesthetic procedure that is essentially 100% effec-
tive. Its use has been enthusiastically embraced by physicians and patients, to the
extent that the name of the first product approved for use in the United States, Botox,
was rapidly incorporated into the popular vernacular. There are two types of type A
toxins, Botox Cosmetic (BoNTA-ONA) and Dysport (BoNTA-ABO), that are FDA ap -
proved for the treatment of glabellar creases; all other indications are considered
off-label.
The dilution and dosage of the two products are distinctly different. Practitioners
must thoroughly understand the reconstitution, indications, technique, therapeutic
benefits, and complications and their management for each of these agents. A type B
alternative is also available for use (Myobloc), or for type A–resistant patients. Al-
though the primary aesthetic use of botulinum toxin remains in the face and neck, ad-
ditional applications are being developed for aesthetic and nonaesthetic indications.
Clinical Caveats
 A new sterile needle and syringe should be used to enter the vial when reconsti-
tuting the drug and for withdrawal of each dose. The manufacturers consider each
botulinum toxin vial to represent a single use.
 If alcohol is used to cleanse the patient’s skin or the rubber stopper on the vial, it
should be allowed to dry before proceeding with the injection to avoid potential
denaturation of the toxin.
 The interval between full botulinum toxin treatment sessions should be at least
3 months.
 The lowest effective dose of the drug should be administered.
 Appropriate supportive care and therapy (epinephrine) should be available and
initiated immediately if anaphylaxis or another severe allergic reaction occurs.
 An anatomic data sheet or some other record is a helpful means of recording the
date of injection, the sites of injection, the number of units used, any concomitant
use of fillers, and the patient response (duration).
 Dilution of the toxin with preserved (benzyl alcohol) 0.9% sodium chloride will
help to relieve pain on injection. Injecting when the muscle is relaxed is also less
painful. The toxin can also be reconstituted with lidocaine, which “previews” the
effect of botulinum toxin, but also impedes the ability of the patient to contract
the muscle after treatment, which may enhance toxin uptake.

Clinical Caveats—cont’d
 Unlike fillers, the skin layer into which botulinum toxin is injected is not as criti-
cal, and results are less potentially operator dependent than with fillers.
 Regularly repeated injections may render the muscle mass smaller, resulting in a
faster onset of action and a longer response, or this effect may result in behavioral
modifications (muscle “retraining”), causing the patient to avoid certain facial move -
ments, thereby naturally improving the area.
 Precise identification of muscular anatomy and needle placement is essential for
a successful outcome. The injector must consider that any effect that botulinum
toxin could have on anatomy may be altered if prior surgery has been performed.
 Problems with dilution occur with greater volumes of diluent, such as more than
5 ml of saline/100 units of Botox Cosmetic, because spread becomes more de-
pendent on excess volume of solution rather than on the drug itself.
 When treating one of the agonist-antagonist muscle groups (frontalis and corru-
gator), for example, for facial reshaping, it may be advisable to counterbalance
the opposing muscle with a small amount of toxin to avoid an imbalance when
movement of an opposing muscle is lost. When counterbalancing muscles is not
an issue (for example, in the orbicularis oris), one should consider the effect that
paralysis of the treated muscle will have on function.
 Facial anatomy (musculature) is similar from one patient to another; the degree
of soft tissue malposition and rhytid formation will vary according to patterns of
muscle usage (animation), resulting in different types of deformities that require
different treatment approaches.
 “Extended” areas of treatment such as the lower half of the face (nasolabial folds,
upper lip lines, marionette grooves, jowls, chin dimpling, and the masseter) should
be weakened rather than paralyzed to avoid a functional imbalance from loss of
muscle activity. In these regions, adjunctive use or primary use of fillers is more
common than botulinum toxin alone as monotherapy.
 Softening the glabellar frown muscle complex that depresses the brow will help
lessen the pull of the antagonist frontalis muscle and reflexly slightly improve
transverse forehead lines.
 Nonresponders who may require additional toxin should be evaluated to deter-
mine whether the response appears to be ineffective because the patient is recruit-
ing surrounding muscles (the “shelf” that appears with smiling below a treated
orbicularis oculi muscle from zygomaticus muscle activity) or a remaining rhytid
that is caused by dermal atrophy, as opposed to an actual therapeutic failure.
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