Botulinum Toxin (Botox)
INTRODUCTION
Botulinum toxin is the product of
Clostridium botulinum. C botulinum bacteria and their
spores are ubiquitous. The bacteria are found in soil and marine
sediments; the spores can be detected on fruits and vegetables and in
seafood. The growing bacteria produces the neurotoxin, botulinum toxin,
which is often referred to as the most poisonous substance known to
mankind. The neurotoxin inhibits the release of acetylcholine and results
in the flaccid paralysis of the affected muscles.
Seven serologically distinct types of botulinum toxin exist: A, B, C1, D, E, F, and G. Botulinum toxin type A (Botox; Allergan, Irvine, Calif) was the first commercially available type in the United States. In Europe, botulinum toxin of the same serotype is marketed by another company (Dysport; Speywood, United Kingdom). Botulinum toxin type B (Myobloc; Elan Pharmaceuticals, San Francisco, Calif) recently became available in the United States.
The separate types of botulinum toxin have different molecular sizes, degrees of activation, and mechanisms of action. Various commercial preparations have different characteristics regarding their clinical performance. Significant research is underway to study the molecular causes of these differences.
This article focuses on the dermatologic applications of botulinum toxin in general. The reader should note that the dermatologic use of botulinum toxin requires an in-depth knowledge of the anatomy and function of the areas treated (eg, in the case of the face, facial muscles, and their relations with the orbit). From the cosmetic point of view, an understanding of the complex functions of the muscles to be injected is especially important.
Botulinum toxin has beneficial effects only on wrinkles caused by muscular contractions. Botulinum toxin is not an appropriate treatment for wrinkles caused by solar exposure or other degenerative processes of the dermal tissues. This article provides only an overview of the technique and of several clinically relevant issues and does not replace hands-on training and experience.
History of the Procedure: During the treatment of blepharospasmus with botulinum A exotoxin, the cosmetic appearance of the glabellar frown lines improve. Thus, the cosmetic effects of botulinum toxin were discovered.
Problem: Botulinum toxin is used in dermatology for the treatment of facial wrinkles caused by muscular contractions. These wrinkles are commonly referred to as crow's feet, frown lines, and bunny lines.
Facial expression is influenced by muscular actions of the face. Both voluntary and involuntary contractions of the muscles play a significant role in expressing various emotions, such as fear, anxiety, and anger. However, the exaggeration of the facial lines can be cosmetically unacceptable or socially undesirable.
Hyperhidrosis, caused by increased local cholinergic activity affecting sweat production, can also be socially unacceptable and may interfere with many daily activities (eg, in the case of palmar hyperhidrosis, with the handling of finer instruments or driving).
Frequency: Facial wrinkling affects almost 100% of the population. However, its perception varies widely across cultures, age and sex groups, as well as occupations and social positions.
Etiology: Two underlying mechanisms cause wrinkles: muscular contractions and solar damage. Botulinum toxin is appropriate only for the treatment of wrinkles caused by muscular action.
Pathophysiology: The neurotoxin inhibits the release of acetylcholine and results in the flaccid paralysis of the affected muscles.
Clinical: Generally, 3 clinical situations of botulism are distinguished: food-borne botulism, wound botulism, and infant botulism. The common mechanism in these disorders is the paralysis of various muscles caused by the botulinum toxin. The paralysis can ultimately lead to the death of the patient. However, one's poison is another’s medicine, because botulinum toxin is useful in the treatment of certain diseases.
The extent and location of the frown lines should be documented with the patient’s face in both a resting position and in an exaggerated expression (eg, frowning, smiling). For comparison, the patient’s facial expressions should be photographed before treatment and at the follow-up examination.
Documenting the patient's concerns about the social implications is important. The desired and realistic results and the patient’s understanding of these results should also be documented.
Hyperhidrosis should be evaluated on a subjective basis. Note the extent to which it interferes with the patient's daily activities and work. List all over-the-counter and prescribed medications that the patient has used to treat this condition. The starch-iodine test is one method for the visual evaluation of the extent and quantity of sweating. Sweating can be quantitatively measured by applying bibulous paper to the area of concern and then weighing the paper after a period of time (see Diagnostic Procedures).
INDICATIONS
The US Food and Drug Administration
(FDA) has approved the use of botulinum toxin for the following purposes
(other regulatory agencies may have additional approved uses): (1) to
temporarily improve the appearance of moderate-to-severe frown lines
between the eyebrows (glabellar lines), (2) to treat strabismus and
blepharospasm associated with dystonia, and (3) to treat cervical
dystonia.
Common indications for the treatment of wrinkles caused by contraction
of the muscles of the face include the treatment of the following:
glabellar frown lines (FDA-approved indication as of 4/15/02), transverse
forehead lines, lateral canthal wrinkles (ie, crow's feet), and medial and
lateral brow lifts.
For an experienced physician, other indications may include the
treatment of the following: wrinkles on the upper lip, nasal scrunching
and flaring, marionette lines, necklines and platysmal bands, mental
creases, and dimpling of the chin. These applications can lead to
complications that interfere with physiologic functions; therefore, some
authors consider them risky. A further indication is the management of
localized axillary or palmar hyperhidrosis that is nonresponsive to
topical or systemic treatment.
Botulinum toxin is also used to treat other conditions. Multiple
off-label uses, including the treatment of focal dystonias, spasticity,
hemifacial spasm, tics, tremors, hyperhidrosis, tension headaches, and
migraines, are reported. These treatment options are considered
experimental.
Corrugator supercilii muscle - Vertical rhytides
When contracted, the bulk of the corrugator supercilii muscle protrudes
at the medial aspect of the eyebrow. The origin of this muscle is
relatively consistent at the junction of the nasal and frontal bones close
to the supramedial orbital rim. A transverse line drawn coronally through
the middle of the eyebrow identifies the horizontal position of the bulk
of the muscle. For the best effect and for avoiding the unwanted injection
of botulinum toxin through the orbital septum, the needle should be
oriented at or slightly above this plane, and the injection should target
the thickest portion of the muscle adjacent to the medial aspect of the
brow. Do not inject points lateral to the midpupillary line.
Procerus muscle - Horizontal rhytides
The procerus muscle is a narrow muscle located in the midline of the
nose; it usually lies 1-4 mm deep to the surface. The muscle is generally
longer in women than in men. The optimal injection site is the midline
just caudal to the nasal root.
Frontal muscle - Horizontal frown lines
Before injecting the frontal muscle, mark the horizontal lines of the
skin. Inject the thickest portions of the muscle at points 1.5-2 cm apart.
Laterally, raise the line of the injections away from the brow to maintain
some function of expression in the lateral part of the brow. To avoid
ptosis, do not inject close to the brow.
Orbicularis oculi muscle - Crow's feet
Mark the lateral canthal line 1 cm lateral to the canthus. Then, the
patient should be asked to squint, and the squint lines above and below
the lateral canthal line are marked. The injections are symmetrically
placed into the muscle on both sides of the face. To avoid problems with
eyelid closure, do not inject too close to the eyelids.
Orbicularis oris and mentalis muscles - Excessive lip pursing
The injection site is the point halfway between the vermilion border of
the lower lip and the inferior edge of the mentum, approximately 0.5-1 cm
medial to the oral commissure. Avoid injecting too close to the lip, and
use only small amounts of the toxin.
Platysma - Platysmal bands
The injections are performed under electromyographic (EMG) control, and
the needle should be inserted perpendicular to the muscle fibers.
Contraindications: Local and systemic
contraindications include the following: (1) wrinkles not caused by
muscular contractions, (2) neuromuscular disorders, (3) known
hypersensitivity to any ingredient in the formulation, (4) pregnancy or
breastfeeding, (5) unrealistic expectations on the patient’s part, and (6)
possible interference with the patient’s work or daily activities due to
changed facial expressions (eg, in the case of public performers).
RELEVANT ANATOMY AND
CONTRAINDICATIONS
Relevant
Anatomy: The most important anatomic units and their related
effects include the following.
Diagnostic Procedures:
The injection can be a single-point injection or a skewered injection.
With the latter method, which is used primarily in the platysma, the
preferred injection site is identified with EMG. The needle is then
inserted parallel to the plane of the muscle, and the injection is
performed while the needle is carefully withdrawn.
Preoperative details: Preoperative details include the
following: identifying contraindications, if any; discussing the realistic
expectations with the patient; identifying the areas to be treated;
locating the targeted muscles; and preparing a plan of injection.
For later comparison, the patient’s face should be photographed before
treatment in both the resting position and in an exaggerated expression (eg, frowning, smiling).
Any makeup should be carefully removed, and the planned injection sites
should be cleaned with isopropyl alcohol.
Intraoperative details: The patient should lie on his
or her back, comfortably propped up.
Postoperative details: To prevent the unwanted
diffusion of botulinum toxin into the adjacent muscles, do not massage the
injection site, and advise patients to avoid doing so as well. Female
patients should not reapply their makeup in the office. All patients
should avoid exertion on the day of treatment.
Follow-up care: Follow up with the patient in 1-2
weeks, and photograph the patient’s face with the same expressions as
those in the preoperative pictures.
Re-treat the patient as needed after the effects diminish.
Ptosis can occur when injections above the brow are too lateral (past
the midpupillary line) or too close to the brow. Some authors use
phenylephrine apraclonidine (Iopidine) eye drops to minimize ptosis.
Delayed eyelid closure, a decreased blink response, and excessive tearing
can occur when injections into the orbicularis oculi muscle in the
temporal region are too close to the eyelid. Asymmetry of the face can
occur because of differences in injection techniques or doses between the
2 sides of the face. Drooling can occur when injections of the orbicularis
oris muscle are too close to the lip.
Systemic complications are possible. Headache has been reported and is
usually transient. Hypersensitivity reactions have not been described.
Antibody development is described in patients receiving high doses of
botulinum toxin (eg, for the treatment of torticollis or dysphonia); as a
result, their muscles become resistant to further therapy. One case of
necrotizing fasciitis occurred after botulinum toxin was injected into a
patient who was immunocompromised.
During the treatment of hyperhidrosis, complications can result from
the use of local anesthetics. Muscular paralysis and a temporary loss of
manual functions are possible alarming complications.
The results are cumulative; repeated treatments tend to lead to
longer-lasting effects. After several injections of botulinum toxin into
the same anatomic region, the underlying muscles may become atrophied.
This effect usually leads to the permanent resolution of the wrinkles.
For comparison, the patient's face should be photographed before
treatment and at follow-up visits.
In the treatment of hyperhidrosis, the use of botulinum toxin results
in dramatic improvement. The treatment must be repeated every 4-6 months.
In addition to the treatment of glabellar lines, the number of
FDA-approved indications for the use of botulinum toxin in cosmetic
applications may increase.
The treatment of wrinkles with botulinum toxin is becoming more
popular, and demand for it is expected to increase. The cosmetic use of
botulinum toxin is essentially controlled by market forces because most
health insurance does not cover it. Economic trends (especially trends in
the amounts of disposable income) and social issues influence the number
of people seeking treatment. Also, the limited number of products and
suppliers affect the current prices of the treatment.
Controversies
What conditions should be treated with injections of botulinum toxin?
Generally, treatment of the glabellar, frontal, and temporal frown lines
is considered safe. Several authorities consider other uses around the
mouth and on the neck risky.
Which preparation should be used? Each preparation is unique, and the
products are not necessarily interchangeable. Different botulinum toxin
serotypes significantly differ in their relative potencies and durations
of action that affect the clinical outcome. Even different preparations of
the same serotype can have marked differences. For instance, 1 U of Botox
has a potency that is approximately equal to 4 U of Dysport. From a
clinical point of view, these preparations may be used interchangeably
with appropriate dosage adjustments. However, the current data are
insufficient to determine whether one product is superior to another.
Both products have advantages and disadvantages. Botox (Allergan) has
been widely used in the United States and Canada for more than a decade.
Its safety is well established. The drawback is that once the contents of
a vial are dissolved, the reconstituted product loses its potency.
Therefore, dermatologists tend to schedule the treatments for several
patients on the same day so that they can use the entire contents of the
vial. This scheduling may be inconvenient for some patients, who may
decide not to proceed.
Myobloc (Elan), when reconstituted, has a shelf life of more than 12
months. This feature is advantageous in terms of patient scheduling.
However, larger volumes of Myobloc may be needed to obtain effects similar
to those of Botox. Antibody formation against this product may occur more
often because of its higher protein content.
REFERENCES
MEDCEU
Continuing Education Courses CEU for Nurses and Healthcare Professional
TREATMENT
Surgical therapy: The
selected areas are treated by injecting either 2-4 units of Botox or
clinically equivalent amounts of Myobloc or Dysport into the thickest part
of the muscle.
All unwanted local effects of
botulinum toxin are generally transient and gradually wear off. However,
some unwanted effects (eg, drooling) can seriously affect the patient’s
everyday activities. As with any injection, pain, mild bruising, and
infection can occur. Diffusion of botulinum toxin can lead to weakness of
the muscles adjacent to the injection site. Therefore, advising the
patient not to massage the injected areas is important.
The effects of botulinum toxin
injections are not immediately noticeable. The full effect is achieved
approximately 3-7 days after treatment, with the peak at around 1 month.
The results last for about 4-6 months with a gradual reappearance of the
wrinkles.
FUTURE AND CONTROVERSIES
Future