Botulinum Toxin Injection for Facial Wrinkles

Botulinum Toxin Injection for Facial WrinklesREBECCA SMALL, MD, University of California–San Francisco, San Francisco, California Botulinum toxin injection for treatment of facial wrinkles is the most frequently performed cosmetic procedure in the United States, and it is one of the most common entry procedures for clinicians seeking to incorporate aesthetic treat- ments into their practice. Treatment of frown lines and crow’s feet, which are the cosmetic indications approved by the U.S. Food and Drug Administration, and horizontal forehead lines, offers predictable results, has few adverse effects, and is associated with high patient satisfaction. Wrinkles are formed by dermal atrophy and repetitive contraction of underlying facial musculature. Botulinum toxin is a potent neurotoxin that inhibits release of acetylcholine at the neuromuscular junction. Injection of small quantities of botulinum toxin into specific overactive muscles causes local- ized muscle relaxation that smooths the overlying skin and reduces wrinkles. Botulinum toxin effects take about two weeks to fully develop and last three to four months. Dynamic wrinkles, seen during muscle contraction, yield more dramatic results than static wrinkles, which are visible at rest. Botulinum toxin injection is contraindicated in per- sons with keloidal scarring, neuromuscular disorders (e.g., myasthenia gravis), allergies to constituents of botulinum toxin products, and body dysmorphic disorder. Minor bruising can occur with botulinum toxin injection. Temporary blepharoptosis and eyebrow ptosis are rare complications that are technique-dependent; incidence declines as injector skill improves. (Am Fam Physician. 2014;90(3):168-175. Copyright © 2014 American Academy of Family Physicians.) B CME This clinical content otulinum toxin injection for treat- temporary chemical denervation. At the cel- conforms to AAFP criteria ment of facial wrinkles is the most lular level, botulinum toxin functions by for continuing medical education (CME). See frequently performed cosmetic cleaving a docking protein (synaptosomal- CME Quiz Questions on procedure in the United States,1 associated protein of 25 kDA [SNAP-25]) on page 145. and it is one of the most common entry pro- the internal surface of neuronal membranes, Author disclosure: No rel- cedures for clinicians seeking to incorporate thereby inhibiting vesicle fusion and release evant financial affiliations. aesthetic treatments into their practice.2 of acetylcholine.7 Botulinum toxin effects See related editorial Botulinum toxin injection, particularly in in the targeted muscles diminish over time ▲ on page 136. the upper one-third of the face, offers pre- as SNAP-25 regenerates, and neuromuscu- Patient information: dictable results,3 has few adverse effects,4 and lar signaling and muscle contractility are ▲ A handout on this topic, is associated with high patient satisfaction.5 restored. written by the author of This article reviews relevant facial anatomy, this article, is available Indications patient selection, complications, and injec- at http://www.aafp.org/ afp/2014/0801/168-s1. tion technique for cosmetic botulinum toxin Botulinum toxin has been used for more html. treatment with a focus on frown lines. It is, than 20 years to treat a variety of conditions however, not intended as a replacement for a including blepharospasm, strabismus, cervi- formal instructional course. cal dystonia, migraines, hyperhidrosis, and muscle spasticity. Botulinum toxin was first Mechanism of Action approved by the U.S. Food and Drug Admin- Wrinkles are formed by dermal atrophy and istration (FDA) for cosmetic use in 2002 as repetitive contraction of underlying facial Botox to treat glabellar complex muscles that musculature. Injection of small quantities form frown lines and in 2013 to treat lateral of botulinum toxin into specific overactive orbicularis oculi muscles that form crow’s muscles causes localized muscle relaxation feet 8 ; it is used off-label for all other cos- that smooths the overlying skin and reduces metic facial indications. It has become the wrinkles.6 treatment of choice for wrinkles occurring Botulinum toxin is a potent neurotoxin in the upper one-third of the face (i.e., frown protein derived from the Clostridium botu- lines, horizontal forehead lines, and crow’s linum bacterium. It exerts its effect at the feet). It is also used in the lower two-thirds neuromuscular junction by inhibiting of the face, but this is more technically chal- the release of acetylcholine, which causes lenging and is an advanced application.9-14 168  American Downloaded Family from the Physician American www.aafp.org/afp Family Physician website at www.aafp.org/afp. Copyright © 2014 American Academy Volume of Family 90, Number Physicians. For3the private, Augustnoncom- ◆ 1, 2014 mercial use of one individual user of the website. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. Corrugator supercilii 12. Depressor supercilii 14. which include Anatomy the corrugator supercilii. but results are slower The muscles contributing to formation of frown lines are and patients may require two or three consecutive August 1. 2014 ◆ Volume 90. Musculature of the face. Hoang D. Temporalis 11. the overlying skin also moves. Contraction of these muscles pulls the brows medi- have soft tissue attachments to skin through the superfi. Horizontal forehead lines (frontalis) 2. Risorius 5. Philadelphia. ally and inferiorly (Figure 315). When facial Patient Selection muscles contract. and depressor super- The muscles of facial expression are unique in that they cilii. Reprinted with permission from Small R. tion and are ideal candidates for treatment (Figure 415). Platysma 6. Orbicularis oris 3. Depressor labii inferioris 8. Zygomaticus minor 1. Chin line (mentalis) alaeque nasi 18. Wrinkles of the face (associated muscle). Number 3 www. Procerus 13. Patients with dynamic wrinkles demonstrate the most ing dynamic wrinkles perpendicular to the direction of dramatic improvements from botulinum toxin injec- muscle contraction (Figure 215). cial muscular aponeurotic system.: Lippincott Williams & Wilkins. Marionette lines (depressor anguli oris) 8. the glabellar complex depressor muscles. Philadelphia. Glabellar wrinkles. Orbicularis oculi 15. Frontalis 10.: Lippincott Williams & Wilkins. Botulinum Toxin Injection 1. Crow’s feet (orbicularis oculi) 4. are vertical lines Patients with static wrinkles that are visible at rest occurring between the medial aspects of the eyebrows. Hoang D. are also candidates (Figure 515). Nasalis 16. which have bony attachments (Figure 115).aafp. Radial lip lines (orbicularis oris) 7. procerus. Pa. Zygomaticus major 2. Modiolus 4. Levator labii superioris 17. Depressor anguli oris 7. Nasolabial folds (levator labii superioris alaequae nasi) 6. Mentalis 9. Levator labii superioris Figure 2. unlike most muscles. Reprinted with permission from Small R. A Practical Guide to Botu- linum Toxin Procedures. Pa. 2012. form.org/afp American Family Physician 169 . Frown lines (glabellar complex) 3. A Practical Guide to Botu- Figure 1. 2012. Bunny lines (nasalis) 5. or frown lines. linum Toxin Procedures. purple = levator muscles. Reprinted from Small R. MD. A Practical Guide to Botu. Functional anatomy of the face.aafp. A Practical Guide to Botulinum Toxin linum Toxin Procedures. Expression lines Muscle Action Frown lines Corrugator supercilii Eyebrows drawn medially Procerus and Eyebrow depressors depressor supercilii Horizontal forehead Frontalis Eyebrow levator lines Crow’s feet Lateral orbicularis Lateral eyebrow oculi depressor Eyebrow lift Superior lateral Superior lateral A orbicularis oculi eyebrow depressor Bunny lines Nasalis Nose drawn up and medially Radial lip lines Orbicularis oris Lip puckering Marionette lines and Depressor anguli Corner of mouth downturned smile oris depressor Gummy smile and Levator labii Central lip levator nasolabial fold superioris alaeque nasi Chin line and Mentalis Chin texture and pebbly chin lower lip levator B Key: orange = depressor muscles.org/afp Volume 90. Pa. MD. Reprinted from Small R. (A) Dynamic frown lines with glabellar complex sphincteric muscles. Philadelphia. 2012. Figure 3. Philadelphia. Procedures. Number 3 ◆ August 1. Ideal candidate for botulinum toxin treatment demonstrating (A) dynamic frown lines with glabellar complex muscle contraction and (B) lack of static lines with glabellar muscles at rest. A B Figure 4. Pa. Copyright © Rebecca Small. gray = Figure 5. muscle contraction and (B) static lines with glabellar mus- cles at rest. Hoang D. Philadelphia. A Practical Guide to Botulinum Toxin Procedures. 2012. Pa. Hoang D. Reprinted with permission from Small R.: Lippincott Williams & Wilkins.: Lippincott Williams & Wilkins. 170  American Family Physician www. Hoang D. Copyright © Rebecca Small. 2012. 2014 .: Lippincott Williams & Wilkins. botulinum toxin treatments for significant improve. myopathies) onabotulinumtoxinA (Botox). Botulinum botulinum toxin protein (A. unrealistic expectations.g.g.aafp. and clinical response. actors. and incobotulinum- Sensitivity or allergy to constituents of the botulinum toxin product toxinA (Xeomin).g. and G). Setting realistic proteins has yet to be determined. dosing. Facial areas of concern are assessed by the physician and linum toxin product. bovine 50 to 60 units‡ $475 for Corporation protein. Botulinum toxin prod- expectations at the time of consultation is important for ucts are not interchangeable because they vary in their patient satisfaction and success with botulinum toxin formulation.org/afp American Family Physician 171 . and 16 through 18. but the clinical significance of complexing procedures to achieve optimal results.g. singers) Dermatoses in the treatment area (e. Information from references 19 and 20. §—OnabotulinumtoxinA to incobotulinumtoxinA strength of action ratio 1:1. There are currently three botu- Infection in the treatment area linum toxin serotype A products approved Keloidal scarring by the FDA for cosmetic use to treat glabel- Neuromuscular disorder (e.g. †—AbobotulinumtoxinA should not be used in patients with cow’s milk protein allergy.15 Deep static lines may not fully respond to proteins.. Contraindications to Botulinum Toxin Injection Body dysmorphic disorder Dependency on facial expression for livelihood (e. antigenicity and hence antibody formation against botu- bination treatment with dermal fillers or other cosmetic linum toxin.14. Botulinum Toxin Injection Table 1. ‡—OnabotulinumtoxinA to abobotulinumtoxinA strength of action ratio 1:2.19. which are summarized in (e.5. August 1. Bell palsy) serotype B is used for medical conditions such Immunocompromised as dystonia. toxin is the only treatment for dynamic wrinkles cur- Botulinum toxin serotype A is the most potent and is used rently approved by the FDA. Cα.21 Lack of complexing proteins may reduce botulinum toxin injection alone and may require com. amyotrophic lateral sclerosis.19. including antici- The C. and body patient simultaneously using a handheld mirror during dysmorphic disorder (Table 1). psoriasis. myasthenia gravis).† lactose monohydrate 300-unit vial Xeomin Merz Pharmaceuticals IncobotulinumtoxinA Human albumin. cow’s milk protein allergy with abobotulinumtoxinA [Dysport]) Table 2. myasthenia lar complex muscles that form frown lines: gravis. whereas incobotulinumtoxinA is free from complexing ments. sucrose 20 to 25 units§ $425 for 100-unit vial *—These starting doses are intended as general guidelines and may be adjusted at the time of treatment based on the patient’s anatomy and glabellar complex muscle mass.g... Contraindications to botulinum toxin injec- tion include keloidal scarring. OnabotulinumtoxinA Human albumin..16-18 the consultation. Areas are priori- Botulinum Toxin Products tized and treatment options discussed. Number 3 www. Inc.. Ona- botulinumtoxinA and abobotulinumtoxinA have hemagglutinin complexing proteins. D. sodium 20 to 25 units $525 for chloride 100-unit vial Dysport Medicis Pharmaceutical AbobotulinumtoxinA Human albumin. neuromuscular disorders Aesthetic Consultation (e. F. abobotu- Pregnancy or breastfeeding linumtoxinA (Dysport).20 All three serotype A products have Unrealistic expectations a 150 kDa core botulinum toxin protein and differ in whether they have complexing pro- Information from references 14. allergy to constituents of botu. eczema) for cosmetic treatments. Treatment options for static Table 2. Cβ. Lambert-Eaton syndrome. treatments. B. E.. teins surrounding the core neurotoxin. Botulinum Toxin Injectable Products Trade Dose for frown name Company Toxin component Other components line treatment* Cost Botox Allergan. 2014 ◆ Volume 90. botulinum bacterium produces eight serotypes of pated results and possible complications. Asymmetries such as uneven eyebrow height and eye aperture are identified. Botulinum toxin Gross motor weakness in the treatment area (e. and injec- tions are placed into the contracted muscles (Figure 6 15). Complications with cosmetic botulinum toxin injec- stituted at the time of treatment into a solution using tions are uncommon and those that occur are usually sterile normal saline.24 Botulinum toxin is commonly used to treat other lines in the upper one-third of the face. and hot tub use) on the Copyright © Rebecca Small.15. or any quent treatment is advised when muscle contraction is injectable procedure. and Figure 6. however. Dilution volumes range from mild and transient.26 These aftercare practices are used Reprinted from Small R. 172  American Family Physician www. Small volumes of botulinum toxin solution are injected. two weeks before treatment.27 Figure 7 shows reduction of areas are typically taken before treatment and two weeks dynamic frown lines one month after treatment of the after treatment. wrinkles include resurfacing procedures (e. microdermabrasion. The botulinum toxin dose tion reactions and undesired botulinum toxin effects injected into glabellar complex muscles for the treatment (Table 3).15. MD.20..g. Photographic complex muscles is seen by the third day after botuli- documentation is recommended with any aesthetic pro.22 glabellar complex muscles with 20 units of onabotu- linumtoxinA. using a 30-gauge.17.aafp. consuming alcohol.15 Return of muscle function is gradual. retinoids). and surgical procedures. bruising can be minimized by visible in the treatment area before facial lines return to advising patients to discontinue aspirin and any medica. beyond three to four months. num toxin injection.23 Anesthesia is not typi. Hoang D.g. such as horizontal forehead lines with injection in the frontalis muscle.28 After multiple treat- tion or dietary supplement that has anticoagulant effects ments. Philadelphia. chemi.15. for some patients. with maximal reduction visible cedure. once clinical effects are evident. Procedure Preparation typically three to four months after treatment.11. Results and Follow-Up cal peels. They are also advised to avoid massaging or applying heat to the treatment area. Pa. one injection in the pro- cerus muscle and two in each of the corrugator super- cilii muscles.Botulinum Toxin Injection The targeted glabellar complex muscles can be iden- tified by having the patient actively frown. 2014 . their pretreatment appearance.: Lippincott Williams & Wilkins. they are Procedures. and crow’s feet with injection in the lateral orbicularis oculi muscles. typically 1 mL or less. treatment intervals can be extended cally necessary for botulinum toxin treatments.30-32 of frown lines is based on the specific botulinum toxin INJECTION REACTIONS product used and mass of the target muscles.29 Botulinum Toxin Injection Complications Botulinum toxin is supplied as a powder and is recon. Dynamic and static photographs of treatment two weeks after injection. Botulinum toxin injection into a contracted gla. Number 3 ◆ August 1. Subse- In preparation for botulinum toxin treatment. to avoid activities that cause flushing (such as exercis- bellar complex muscle.. botulinum toxin effects may be prolonged and. There are five injection sites. Table 2 lists starting doses used for treatment of frown lines with the Botulinum toxin injections are performed using small- three FDA-approved botulinum toxin products. topical products Partial reduction in function of the targeted glabellar (e.20 gauge needles to minimize discomfort and bruising.org/afp Volume 90. A Practical Guide to Botulinum Toxin to reduce potential spread of the toxin.19.30 They can be categorized into injec- 1 to 4 mL per 100-unit vial. day of treatment. lasers). 2012.17 Aftercare Patients are advised to avoid lying supine following treatment for four hours. ing heavily. not supported by randomized controlled trials. 1-inch needle.10.25 Localized burn- ing or stinging sensation during injection is commonly reported and resolves within a few minutes. Number 3 www.aafp.35 Erythema. but can occur with any procedure that breaches the skin barrier. and may be caused by nerve Injection trauma. Mild erythema.33 There are reports Copyright © Rebecca Small. incidence declines as Antibodies against botulinum toxin injector skill improves. Philadelphia. MD. Application of ice and pressure to a bruise Figure 7. 2012.: Lippincott Williams & Wilkins. Vasovagal episodes associated with severe anxiety can Injection reactions occur and it is advisable to have appropriate emergency Anxiety or vasovagal episode protocols and medications available in the office when Ecchymosis performing injection procedures. Dynamic frown lines with glabellar complex can minimize enlargement. Hoang D. oids may be used to manage headaches based on severity. Botulinum Toxin Injection A Figure 8. MD. 2012. Eyebrow ptosis seen as a 2. Hoang D.30.: Lippincott Williams & Wilkins. A Practical Guide to Botulinum Toxin weeks. Blepharoptosis is caused by deep migration Undesired eyebrow shape or unsatisfactory result of botulinum toxin through the orbital septum fascia to the levator palpebrae superioris.31 Temporary blepharoptosis Blepharoptosis (upper eyelid droop) is uncommon (1% to 5%) but is Distant spread from the injection site distressing for patients. Reprinted from Small R. Paresthesia or dysesthesia in Table 3. resolve a few days after treatment. These compli- Allergic reaction cations are technique-dependent.org/afp American Family Physician 173 .34 Nonsteroidal anti-inflammatory drugs or opi- Procedures. Anxiety with injection procedures is common. most are mild and spontaneously onabotulinumtoxinA (Botox) treatment. A Practical Guide to Botulinum Toxin Procedures. and are primar- Paresthesia or dysesthesia ily caused by temporary denervation of adjacent muscles Undesired botulinum toxin effects outside of the intended treatment area.to 3-mm lowering of the affected eyelid that Facial asymmetry is most marked at the end of the day with muscle fatigue Medication interactions (Figure 815). Pa. Complications with Botulinum Toxin the treatment area is rare. Pa. Philadelphia. of idiosyncratic severe headaches lasting two to four Reprinted from Small R. Right-sided blepharoptosis three weeks after botulinum toxin treatment of the glabellar complex for frown lines. and tenderness Headache UNDESIRED EFFECTS Infection Complications related to botulinum toxin effects occur Pain less frequently than injection reactions. edema.15 Headaches can occur muscle contraction (A) before and (B) one month after with facial injections. Copyright © Rebecca Small. 2014 ◆ Volume 90. Infection is rare. edema.9 It is almost always unilateral. Incidence of blepharoptosis is reduced by plac- ing botulinum toxin injections at least 1 cm above the August 1. and tenderness at injection sites are expected and resolve within a day. muscle. Bruising is com- mon and ranges from pinpoint needle insertion marks to quarter-sized ecchymoses that can take up to two weeks B to resolve. an upper eyelid levator Information from references 30 through 32. disease-oriented evidence. rather than of Family and Community Medicine at the University of California–San diphenhydramine (Benadryl) because of its anticho. edema. Botulinum toxin serotype A is safe and A 9. 24. B = inconsistent or limited- undesired eyebrow shape are usually related quality patient-oriented evidence. with signs of urticaria. 21 tion apraclonidine 0. 2014. 23 upper eyelid.. go to http://www. 21.me).org/afpsort. ptosis.43 of adjacent muscles are temporary and will spontane- ously resolve as botulinum toxin effects diminish. 13. an adrenergic levator muscle of the In preparation for botulinum toxin C 17.covered by insurance. Number 3 ◆ August 1. facial indications. however. Apraclonidine is reserved for discontinue aspirin and any medication refractory cases and should be used with or dietary supplements associated with caution because it can exacerbate or unmask bruising for two weeks before treatment. with injected botulinum toxin. MD.025%/pheniramine 0. 12.38. and Essential Evi- and muscle relaxants. Capitola. Also searched were the FDA website. 2014.g. and April 24. Case reports of adverse effects due to 40 distant spread from the injection site have been reported Address correspondence to Rebecca Small. efficacy. Am Fam Physician.. or horizontal forehead lines). and reviews. the frontalis muscle. American Society for Aesthetic Plastic Surgery. is an associate clinical professor in the Department (Solu-Medrol) is advised when indicated. Distant spread has not been reported with 1.surgery. tive. protein is a constituent. 300 units in able from the author. underlying glaucoma. usual to unintended botulinum toxin effects in practice. Search dates: February 2.36 Medications that inhibit neuromuscular signaling frown lines.14.of botulinum toxin units used or on the area treated (i. and UpToDate. which can render treatments ineffec.80(11):1231-1237. which include generalized muscle weakness. and possibly ana- phylaxis. good-quality patient-oriented evidence. C = consensus. such as aminoglycosides. Cosmetic botulinum toxin treatments are not Other rare complications associated with botuli.Botulinum Toxin Injection supraorbital ridge at the midpupillary line when treating the corrugator muscles. There are case reports of botulism 2. and death from respiratory com- promise. dysphagia. muscle. these instances 2009. such as over-the-counter naphazo- line 0. Facial Financial Considerations and Coding asymmetry can result from uneven dosing of botuli. AbobotulinumtoxinA is contraindicated in num toxin. clinical trials.The current procedural terminology (CPT) designation num toxin.5% (Iopidine). resulting in elevation of the treatment. Data Sources: A PubMed. 174  American Family Physician www.aafp. Some of these compli- cations can be corrected with botulinum toxin injection in muscles that antagonize the affected involved research-grade botulinum toxin that was not muscles. Evidence thalmic solutions that have alpha-adrenergic Clinical recommendation rating References effects. For information about the SORT evidence rating system.e. Reprints are not avail- with large doses of botulinum toxin (e. quinidine. linergic effects. crow’s feet.Francisco School of Medicine and the director of medical aesthetic training at Natividad Medical Center in Salinas.. expert opinion. Ste. Consistent technique and careful attention for botulinum toxin injection of the face is chemodenerva- to injection volumes at the time of treatment can reduce tion of muscles innervated by the facial nerve (CPT code: the incidence of asymmetries. safety.The Author ications such as epinephrine and methylprednisolone REBECCA SMALL. aesthetic procedure textbooks. may potentiate botulinum toxin dence search was completed in Clinical Queries using the key terms botuli- effects.org/media/ cosmetic use of botulinum toxin for frown lines or other statistics. 64612). Cochrane database. Aesthetic procedures in office practice. REFERENCES respiratory difficulties.42.17 SORT: KEY RECOMMENDATIONS FOR PRACTICE Blepharoptosis may be treated using oph. patients should be advised to upper eyelid. 2014 . anticholinergics. complications caused by involvement approved or intended for human use. effective for reduction of frown lines. immediate hypersensitivity and allergic reactions may occur. 25 medications cause contraction of Müller effective for reduction of crow’s feet. The search included 37 patients with cow’s milk protein allergy because bovine meta-analyses. Using standard emergency protocols and med. randomized controlled trials. Fees for injections range from $250 num toxin injections include formation of antibodies to $550 per treatment area and are based on the number (less than 1%). Small R. 20. 246. or case series. the calves). cosmetic. however. dysarthria.3% or prescrip. http://www. CA 95010 (e-mail: [email protected]/afp Volume 90. Both Botulinum toxin serotype A is safe and A 12. 820 Bay Ave. 2013. Cosmetic Surgery 41 National Data Bank statistics 2013. POEMs.39 Although extremely rare. and frown lines. urinary incontinence.aafp. MD. Eyebrow ptosis and 32 A = consistent. Calif. Accessed February 26. : Group. toxinA (Dysport) in the treatment of forehead. wood Unit) –Part I: upper facial wrinkles. tion with botulinum a exotoxin: report of 5 cases. and periorbital 34.fda. Hoang D. Pharmacology of therapeutic botulinum toxin 2010. 2007. Carruthers A. 2012 http://pi.fda. Cirillo P. Alam M. Lowe NJ. 2010. internally con. 42. Scuderi N. September 11. 2003. A prospective. et al. Ascher B. International consensus recom. Curr Med Res Opin. Bilateral.org/afp American Family Physician 175 . Geriatrics. 30. 2010. Toback SL.pdf. Triple-blind. Pa. 2014. 2014.24(11):1278-1284. Carruthers A.aafp. 2002.46(6):840-849. Irvine. Ray BB. Carruthers JA. Derksen DJ.: Elsevier/Saunders.: Elsevier/Saunders.S. Patient-reported benefit and satis. Carruthers J. 2012:363-372. use [prescribing information]. In: Pfenninger JL. Pa.: Elsevier/Saunders. Konrad H. 41. Plast Reconstr Surg. 2011. botulinum toxin.3(2):179-189. Cavallini M. Moore D. Marcus S. Philadelphia. Blasi J. http://www. 2012:248-258. In: Pfenninger JL.36(suppl 4):2155-2160. J Am Acad Dermatol.: Mosby Else- bellar lines: a review of the efficacy and safety of currently available vier. Stotland MA. Botulism in 4 adults following J. highly concentrated botulinum Office Practice. Dermatol Surg. et al. He WQ. 32. Michaels BM. 2002. domized. izing antibody conversion with onabotulinumtoxinA (BOTOX®) across mendations on the aesthetic usage of botulinum toxin type A (Spey. Botulinum toxin: examining duration of effect in facial aes- ment of glabellar lines. 9. Pa. 2008. Bowen B. Grablowitz D. free from complexing proteins. matol Surg. double-blind.67(10):1855-1856. Pfenninger J. Kolluru A. glabellar. Pfenninger 43. Patel RK. Talarico S. Fagien S. rmationforHeathcareProfessionals/ucm174949. Eko FN. Silver Springs.: Allergen.29(23):1761-1768. focal injection of botulinum toxin. Meta-analysis of neutral- 14. Severe respiratory failure after injection 21. Fowler GC. Nong LB. August 1. in patients with crow’s feet. and insights with the use of 2003. double-blind.31(5):369-371. Inc. Philadeplhia. Botanicals can affect surgical outcomes and follow-up. Calif. Tan ET. 2004. Dysport (abobotulinumtoxin A) injection [prescribing information]. Cohen JL. 2007. cleaves the synaptic protein SNAP-25. of botulinum toxin: case report and review of the literature [in Chinese]. Yamauchi PS. Pa. Carruthers A. Zhongus Jie He He Hu Xi Za Zhi. Fowler GC. 2005. Am Fam botulinum toxin type A in the treatment of glabellar frown lines. 2011. review and meta-analysis. Compositional differences among commer- otulinumtoxin A). Compar- glabellar rhytides: results from a prospective open-label study.6(3):141-150. 17. et al. Stuhlberg D. Dietary supplements in primary upper face.allergan. Maslanka SE. 38. Naumann M. Small Surg. Dermatol Surg. Lask GP. 37. Managing adverse events associated with botuli- domized comparison of 3 doses of botulinum toxin type A and placebo num toxin type A: a focus on cosmetic procedures. Botulinum Toxin. Chapman ER. preparations. Carruthers J. Severe. Rapid onset feet lines [news release]. for intramuscular 2010.fda.20(7):981-990. multiple indications. www. FDA approves Botox Cosmetic to improve the appearance of crow’s 27. Physician. 13. Botulinum toxin type A for facial rejuvenation. trolled comparative study between abobotulinumtoxinA and onabotu. Noninferiority of incobotu. Dressler D. Botox Consensus Group. Benecke R. 39. ary 26. Dermatol Surg. Fundarò SP. Small R. Xu YH.medicis. Link E. Food and Drug Administration. Botulinum neurotoxin A selectively eds. et al. Pa. Mov Disord. McArdle J. Dermatologic and Cosmetic Procedures in Office Practice. Pfenninger and Fowler’s Procedures for Primary Care. Consen. aesthetic treatments: a systematic review of clinical studies. Botulinum Toxin Injection 3. Clin Dermatol. Ciocon JO.: Lippincott Williams & Wilkins. Ciocon DG. Inc. BOTOX Glabellar Lines I Study ed.pdf. Food and Drug of response and patient-reported outcomes after onabotulinumtoxinA Administration. Small R. discussion 1394.: U.29(5):461-467. 31. Kowalski JW. Naumann M. Prospective random. faction with botulinum toxin type A treatment of moderate to severe 25. Accessed April 18. 10. Am J Clin Dermatol. 8.12(6):377-388. Philadelphia. Kamin SS. eds. J Am Acad Dermatol. compared with another 35. 2007. Wollina U. Kassir R. J Eur Acad Dermatol Venereol. 28. 2006. Klein AW.S. In: Usatine R. 1993.22(1):66-75. JAMA. 2004.htm. a in female subjects with horizontal forehead rhytides. Kassir M. Small R. Cassuto D.us/ ary 20 2013. UCM165110. Arndt KA.. abobotulinumtoxinA (marketed as Dysport) and rimabotulinumtoxinB sus recommendations on the use of botulinum toxin type a in facial (marketed as Myobloc). Complications of injectable fillers and neurotoxins. 2011. randomized.: Medicis Aesthetics. Hartstein ME. 2011:1507-1509.75(11):1679-1684. Md. J Drugs Dermatol.htm. Safety of botulinum toxin A in 2004. 4 0. Severe botulism after 2013. Zschocke I. Kollhorst B. thetic applications.36(suppl 4):2146-2154. eds. marketDrugSafetyInformationforPatientsandProviders/DrugSafetyInfo 18. 12. ran.pdf.46(1):62-65. 2012. http://www. dose-ranging study of botulinum toxin type Dermatol Ther. Klein AW. parallel.com/assets/pdf/botox_cosmetic_pi. Ariz. et al. Beer KR. 2013. Carruthers J.296(20):2476-2479. The Essential Guide to Primary Care Procedures. eds. Complications. Philadelphia.S. Am J Clin Dermatol. Dessy LA.gov/Drugs/DrugSafety/Post aesthetics. Dermatologic and Cosmetic Procedures in cosmetic injections with an unlicensed.11(3):183-199. Accessed Febru- Philadelphia. Am J Clin Dermatol. 22(5):407-412. care.40(5):525-536. 2006. A Practical Guide to Botulinum Toxin Procedures. 2011.114(6 suppl):1S-22S.59(9):20-24. 2004. A multicenter. Callander MJ. Stuhlberg D. Small R.25(13):2211-2218. Number 3 www. Accessed April 18. Adigun CG. Galindo DJ. 2009:200-213. R. linumtoxinA. 2002. Accessed Febru- Scottsdale. et al. 2013. products. Aesthet Surg J. double-blind. Botox cosmetic (onabotulinumtoxinA) for injection.32(1):96-102. discussion 556. The use of botulinum toxin type A in the 23.47(6):834-840. U. linumtoxinA for the treatment of facial rhytids. Nature.group. 7. Der.24(6):524-536. intractable headache after injec- wrinkles.gov/downloads/Drugs/DrugSafety/ cially available botulinum toxin type A. 4. 36. Medical emergency preparedness in office practice. Curr Opin Ophthalmol. Pa. Mazzocchi M. Botulinum toxin for gla. Dermatol 24.gov/newsevents/ treatment of moderate-to-severe glabellar lines. Chertow DS. Csank GA. Accessed February 26. Matarasso SL. prospective. Flynn TC. http://www. ran. et al. placebo-controlled Lippincott Williams & Wilson. Wissmüller E. Safety of botulinum toxin type A: a systematic ized comparison of onabotulinumtoxinA (Botox) and abobotulinum. 2014. Bakshi E. Jankovic J. Contraindications and complications with the use of botuli. Karim H. 22. 2014. double-blind. et al. 2012. Fallico N. 2012:230-240. feet: a split-face. 11.29(5):549-556. Zimmerman. Information for healthcare pro- num toxin.120(5):1386-1393. Souayah N. dysport. http:// 15. 2006. Menter MA. Medication guide: Dysport (abob- 19. Lowe NJ. 16. 2014. Brin MF. Williams S.14(3):253-260. Botolinum toxin. Disabil Rehabil. preparation. fessionals: onabotulinumtoxinA (marketed as Botox/Botox Cosmetic). delphia. 2014 ◆ Volume 90. Prager W. 2010. Phila- 5. Plast ison of two botulinum toxin type A preparations for treating crow’s Reconstr Surg. adverse reactions.10(1):39-44. In: Usatine R. Rubin A. Edward M. Small R. Cox SE. Dermatol Ther (Heidelb). 6. and Fowler’s Procedures for Primary Care. Food and Drug Administration. 29.. Aesthetic Principles and Consultation.. Dover JS. J Am Acad Dermatol. Sattler G. newsroom/pressannouncements/ucm367662.365(6442):160-163. Anaphylaxis. Facial Plast Surg Clin North Am. 33. Neurology. proof-of-concept study. U. Ryb GE. Carruthers JD. 26. study of the efficacy and safety of botulinum toxin type A in the treat. James SP. Boyd C. In: Mayeaux E. Pfenninger 20.