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 produce 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; Solstice Neurosciences, San Francisco, Calif) is also 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. For excellent patient education resources, visit eMedicine's Procedures Center. Also, see eMedicine's patient education article BOTOX® Injections.
Several eMedicine articles address botulinum toxin – related procedures, as follows:
- Botulinum Toxin (BOTOX®): Dystonia Treatment
- Botulinum Toxin in Pain Management
- Botulinum Toxin: Overview
- BOTOX® Injections to Improve Facial Aesthetics
- BOTOX® Injections
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.
Presentation
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).
BOTOX® is indicated (1) for the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia, (2) for the treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents, (3) for the treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients aged 12 years and older.
BOTOX® Cosmetic is indicated for temporary improvement in the appearance of moderate-to-severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients.
Myobloc Injectable Solution (botulinum toxin type B) in the United States and Canada and Neurobloc in Europe is indicated for the treatment of patients with cervical dystonia to reduce the severity of abnormal head position and pain associated with cervical dystonia.1
Common uses of botulinum toxin A include the treatment of wrinkles caused by contraction of the muscles of the face, which includes glabellar frown lines,2,3 transverse forehead lines, lateral canthal wrinkles (ie, crow's feet), and medial and lateral brow lifts.
For an experienced physician, other indications may include treatment of the following: wrinkles on the upper lip, nasal scrunching and flaring, marionette lines, necklines and platysmal bands,4 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.5,6,7
Botulinum toxin is also used to treat other conditions. Multiple off-label uses, including the treatment of palmar and plantar hyperhidrosis, focal dystonias, spasticity, hemifacial spasm, tics, tremors, tension headaches, and migraines, are reported.8 These treatment options are considered experimental.
Relevant Anatomy
The most important anatomic units and their related effects include the following.
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 control, and the needle should be inserted perpendicular to the muscle fibers.
Axilla
Prior to the injections, an iodine starch test is recommended. The hyperhidrotic areas are delineated by a deep blue-black color. To ensure intradermal placement of the botulinum toxin, each dose should be injected with the needle at a 45° angle to the skin surface. The beveled side should point upwards to minimize leakage. The injection sites should be evenly spaced, taking into consideration that each injection site has a ring of effect of up to approximately 2 cm in diameter. The recommended total dose is 50 U per axilla. Avoid marking the injection sites with ink; if ink is used, do not inject directly through the mark, which may create a permanent tattoo.
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 patient expectations, (6) possible interference with the patient's work or daily activities due to changed facial expressions (eg, in the case of public performers), and (7) infection at the proposed injection site(s).
More on Botulinum Toxin |
 Overview: Botulinum Toxin |
| Workup: Botulinum Toxin |
| Treatment: Botulinum Toxin |
| Follow-up: Botulinum Toxin |
| References |
| Next Page » |
References
Berman B, Seeberger L, Kumar R. Long-term safety, efficacy, dosing, and development of resistance with botulinum toxin type B in cervical dystonia. Mov Disord. Feb 2005;20(2):233-7. [Medline].
Carruthers JD, Carruthers JA. Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol. Jan 1992;18(1):17-21. [Medline].
Macdonald MR, Spiegel JH, Raven RB, Kabaker SS, Maas CS. An anatomical approach to glabellar rhytids. Arch Otolaryngol Head Neck Surg. Dec 1998;124(12):1315-20. [Medline].
Matarasso A, Matarasso SL, Brandt FS, Bellman B. Botulinum A exotoxin for the management of platysma bands. Plast Reconstr Surg. Feb 1999;103(2):645-52; discussion 653-5. [Medline].
Farrugia MK, Nicholls EA. Intradermal botulinum A toxin injection for axillary hyperhydrosis. J Pediatr Surg. Oct 2005;40(10):1668-9. [Medline].
Heckmann M, Ceballos-Baumann AO, Plewig G. Botulinum toxin A for axillary hyperhidrosis (excessive sweating). N Engl J Med. Feb 15 2001;344(7):488-93. [Medline].
Naver H, Swartling C, Aquilonius SM. Palmar and axillary hyperhidrosis treated with botulinum toxin: one-year clinical follow-up. Eur J Neurol. Jan 2000;7(1):55-62. [Medline].
Schulte-Mattler WJ, Wieser T, Zierz S. Treatment of tension-type headache with botulinum toxin: a pilot study. Eur J Med Res. May 26 1999;4(5):183-6. [Medline].
Matarasso SL, Matarasso A. Treatment guidelines for botulinum toxin type A for the periocular region and a report on partial upper lip ptosis following injections to the lateral canthal rhytids. Plast Reconstr Surg. Jul 2001;108(1):208-14; discussion 215-7. [Medline].
Smith ME, Ford CN. Resistance to botulinum toxin injections for spasmodic dysphonia. Arch Otolaryngol Head Neck Surg. Apr 2000;126(4):533-5. [Medline].
Latimer PR, Hodgkins PR, Vakalis AN, Butler RE, Evans AR, Zaki GA. Necrotising fasciitis as a complication of botulinum toxin injection. Eye. 1998;12 ( Pt 1):51-3. [Medline].
Chertow DS, Tan ET, Maslanka SE, et al. Botulism in 4 adults following cosmetic injections with an unlicensed, highly concentrated botulinum preparation. JAMA. Nov 22 2006;296(20):2476-9. [Medline].
Connor KM, Cook JL, Davidson JR. Botulinum toxin treatment of social anxiety disorder with hyperhidrosis: a placebo-controlled double-blind trial. J Clin Psychiatry. Jan 2006;67(1):30-6. [Medline].
Odergren T, Hjaltason H, Kaakkola S, et al. A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport and Botox in the treatment of cervical dystonia. J Neurol Neurosurg Psychiatry. Jan 1998;64(1):6-12. [Medline].
Baumann L, Slezinger A, Halem M, et al. Pilot study of the safety and efficacy of Myobloc (botulinum toxin type B) for treatment of axillary hyperhidrosis. Int J Dermatol. May 2005;44(5):418-24. [Medline].
Nelson L, Bachoo P, Holmes J. Botulinum toxin type B: a new therapy for axillary hyperhidrosis. Br J Plast Surg. Mar 2005;58(2):228-32. [Medline].
Chapman MA, Barron R, Tanis DC, Gill CE, Charles PD. Comparison of botulinum neurotoxin preparations for the treatment of cervical dystonia. Clin Ther. Jul 2007;29(7):1325-37. [Medline].
Trindade de Almeida AR, Marques E, de Almeida J, Cunha T, Boraso R. Pilot study comparing the diffusion of two formulations of botulinum toxin type A in patients with forehead hyperhidrosis. Dermatol Surg. Jan 2007;33(1 Spec No.):S37-43. [Medline].
Annese V, Bassotti G, Coccia G, et al. Comparison of two different formulations of botulinum toxin A for the treatment of oesophageal achalasia. The Gismad Achalasia Study Group. Aliment Pharmacol Ther. Oct 1999;13(10):1347-50. [Medline].
Aoki KR. Pharmacology and immunology of botulinum toxin serotypes. J Neurol. Apr 2001;248 Suppl 1:3-10. [Medline].
Armstrong MW, Mountain RE, Murray JA. Treatment of facial synkinesis and facial asymmetry with botulinum toxin type A following facial nerve palsy. Clin Otolaryngol Allied Sci. Feb 1996;21(1):15-20. [Medline].
Bigalke H, Wohlfarth K, Irmer A, Dengler R. Botulinum A toxin: Dysport improvement of biological availability. Exp Neurol. Mar 2001;168(1):162-70. [Medline].
Braune C, Erbguth F, Birklein F. Dose thresholds and duration of the local anhidrotic effect of botulinum toxin injections: measured by sudometry. Br J Dermatol. Jan 2001;144(1):111-7. [Medline].
Brin MF. Botulinum toxin: chemistry, pharmacology, toxicity, and immunology. Muscle Nerve Suppl. 1997;6:S146-68. [Medline].
Huang W, Foster JA, Rogachefsky AS. Pharmacology of botulinum toxin. J Am Acad Dermatol. Aug 2000;43(2 Pt 1):249-59. [Medline].
Lowe NJ. Botulinum toxin type A for facial rejuvenation. United States and United Kingdom perspectives. Dermatol Surg. Nov 1998;24(11):1216-8. [Medline].
Matarasso SL. Complications of botulinum A exotoxin for hyperfunctional lines. Dermatol Surg. Nov 1998;24(11):1249-54. [Medline].
Naumann M. Evidence-based medicine: botulinum toxin in focal hyperhidrosis. J Neurol. Apr 2001;248 Suppl 1:31-3. [Medline].
Naumann M, Jankovic J. Safety of botulinum toxin type A: a systematic review and meta-analysis. Curr Med Res Opin. Jul 2004;20(7):981-90. [Medline].
Further Reading
Keywords
botulinum toxin, botulinum toxin type A, botulinum toxin type B, BOTOX®, BOTOX, Myobloc, Elan, Neurobloc, Dysport, Clostridium botulinum, C botulinum, botulism, wrinkles, crow's feet, frown lines, bunny lines
