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91 Kurzen H, Kari U Novel aspects in cutaneous biology of acetylcholine synthesis and acetylcholine receptors Exp Dermatol 2004;13:27 92 Chernyavsky AI, Arredondo J, Wess J, et al Novel signaling pathways mediating reciprocal control of keratinocyte migration and wound epithelialzation through M3 and M4 muscarinic receptors J Cell Biol 2004;166:261 93 Shapiro E, Miller AR, Lepor H Down regulation of the muscarinic cholinergic receptor of the rat prostate following castration J Urol 1985;1:179 94 Toyoda M, Morohashi M Pathogenesis of acne Med Electron Microsc 2001;34:29 95 Lim EC, Raymond CS Botulinum toxin injections to reduce adiposity: possibility, or fat chance Med Hypotheses 2006;67:1086 96 Balbo SL, Mathias PC, Bonfleur ML, et al Vagotomy reduces obesity in MSGtreated rats Res Commun Mol Pathol Pharmacol 2000;108:291 97 Jones PP, Davy KP, Alexander S Agerelated increase in muscle sympathetic nerve activity is associated with abdominal adiposity Am J Physiol 1997;272:E976 98 Lindmark S, L nn L, Wiklund U, et al Dysregulation of the autonomic nervous system can be a link between visceral adiposity and insulin resistance Obes Res 2005;13:717
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99 Lim EC, Seet RC Botulinum toxin, Quo Vadis Med Hypotheses 2007;69:718 100 Rubegni P, Fimiani M, Tosi GM, et al Conjunctival edema and alopecia of the external third of the eyebrows in a patient with Meige syndrome Graefes Arch Clin Exp Ophthalmol 2000;238:98 101 Kowing D Madarosis and facial alopecia presumed secondary to botlinum a toxin injections Optom Vis Sci 2005;82:579 102 Hasse S, Chernyavsky AI, Grando SA, et al The M4 muscarinic acetylcholine receptor plays a key role in the control of murine hair follicle cycling and pigmentation Life Sci 2007;80;2248 103 Kurzen H, Berger H, Jager C, et al Phenotypical and molecular profiling of the extraneuronal cholinergic system of the skin J Invest Dermatol 2004;123: 937 104 Cutrer FM, Pittelkow MR Cephalalgic alopecia areata: a syndrome of neuralgiform head pain and hair loss responsive to botulinum A toxin injection Cephalalgia 2006;26:747 105 Carruthers A, Carruthers JD Botulinum toxin type A in facial aesthetics an update US Dermatology Review 2006; 1-5 106 Patel MP, Talmor M, Nolan WB Botox and collagen for glabellar furrows: advantages of combination therapy Ann Plast Surg 2004;52:442
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107 Carruthers J, Carruthers A, Zelichowska A The power of combined therapies: Botox and ablative facial laser resurfacing Am J Cosm Surg 2000;17:129 108 Carruthers J, Carruthers A The effect of full-face broadband light treatments alone and in combination with bilateral crow s feet botulinum toxin type A chemodenervation Dermatol Surg 2004;30:355 109 Lee SK Antibody-induced failure of botulinum toxin type A therapy in a patient with masseteric hypertrophy Dermatol Surg 2007;33:S105 110 Pellett S, Tepp WH, Clancy CM, et al A neuronal cell-based neurotoxin assay for highly sensitive and specific detection of neutralizing serum antibodies FEBS Lett 2007;581:4803 111 Dressler D Clinical presentation and management of antibody-induced failure of botulinum toxin therapy Mov Disord 2004;19(suppl 8):S92 112 Guyuron B, Huddleston SW Aesthetic indications for botulinum toxin injection Plast Reconstr Surg 194;93:913 113 Borodic G Myasthenic crisis after botulinum toxin Lancet 1998;352:1832 114 Cox NH, Duffey P, Royle J Fixed drug eruption caused by lactose in an injected botulinum toxin preparation J Am Acad Dermatol 1999;40:263
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CHAPTER 23 Dermal Fillers
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Leslie Baumann, MD Marianna Blyumin, MD Sogol Saghari, MD HISTORY
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In 1893, by transplanting fat from the arms into facial defects, Neuber became the first physician to practice soft tissue augmentation1 In the middle of the 20th century, soft tissue augmentation could best be characterized by the use of silicone Although popular in the 1940s and 1950s, silicone use was associated with the development of foreign body granulomas, which ultimately prompted the banning of silicone in 1992 until a new form of the substance (intended for ophthalmologic use) was approved by the United States Food and Drug Administration (FDA) in the late 1990s In the meantime, though, the field of soft tissue augmentation had come into its own, in the 1970s, with the introduction by Stanford University researchers of animal-derived collagen implants2 By the 1980s, the use of collagen injections for wrinkles had entered the mainstream While Americans were enjoying the benefits of bovine collagen fillers (ie, Zyderm and Zyplast), other countries began to experiment with dermal HA fillers such as Hylaform and later Restylane in the mid to late 1990s The beginning of the 21st century ushered in the introduction of newer nonbovine collagen fillers, CosmoDerm and CosmoPlast, and HA fillers, such as Captique and Juv derm, as well as other synthetic fillers, Sculptra, Radiesse, and Artefill into the United States market With different forms of soft tissue augmentation agents currently available in the United States and others in the pipeline, selecting the appropriate filler is challenging for physicians and patients alike In order to achieve optimal cosmetically-pleasing results, it is incumbent upon dermatologists to obtain thorough comprehension of the characteristics of available fillers, their indications, contraindications, benefits and drawbacks, and ways to resolve potential complications In this chapter, we will review the basics behind the art and science of the broad array of dermal fillers on the market in the United States This will be preceded by a brief discussion of regulatory issues and the patient evaluation and consultation approval for a dermal filler must satisfy the intense safety and efficacy criteria including nonteratogenicity, nonmigration, noncarcinogenesis, biocompatibility, and optimal purity, as well as reproducible and durable efficacy in correcting skin defects Unfortunately, some physicians and physician extenders choose to use dermal filling substances that have not yet received FDA approval for any indication This is not advisable for several reasons including the fact that it is illegal and that the safety of these products has not been established With the multitude of safe, efficacious, and durable fillers on the market, there is no need or justifiable reason to use unapproved dermal fillers in the US
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The dermal filler market is rapidly growing worldwide According to the American Academy of Aesthetic Plastic Surgeons, 1,448,716 people received hyaluronic acid (HA) injections by plastic surgeons in 2007 (Table 23-1) The actual number is likely much higher when factoring in procedures performed by dermatologists and other aesthetically oriented physicians and physician extenders Although collagen products (Zyplast and Zyderm) were the first dermal fillers to become widely available, collagen fillers have largely been replaced by HA fillers The ultimate goal of dermal fillers is to smooth out wrinkles and folds, even out scars, volumize furrows and sunken valleys, contour unevenness and laxity, and sculpt skin into a 360-degree, rejuvenated look Over the last quarter century, several kinds of products suitable for soft tissue augmentation have become available, with intense industry research yielding more and more filler options with increasing regularity Different regulatory mechanisms usually leave the US a few months or years behind other developed countries in making the latest products available to patients
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