Caveat Emptor (Buyer Beware)

THE COSMETIC use of botulinum toxin is now well established. The extended clinical use, multiple publications, and recent Food and Drug Administration (FDA) approval have combined to create this fact, demonstrated in the current media frenzy. But will this situation increase the number of novice injectors and hence increase the incidence of adverse effects, amplifying the "BOTOX backlash" that we are seeing? Will we now see a rash of eyelid and eyebrow ptosis? An epidemic of paralyzed and patulous perioral and cervical muscles? BOTOX losing its shiny reputation as the New Age wonder drug due to an epidemic of avoidable complications? An example of what can happen comes from the scientific basis of the FDA approval. Presumably, the manufacturers of BOTOX (Allergan, Inc, Irvine, Calif) selected physicians they believed were experienced in the cosmetic use of botulinum toxin to perform the FDA studies. And yet, one half of the study population had an eyelid ptosis rate of over 5.4%, which is unacceptably high, compared with the approximately 1% in the other half of the study.¹ This demonstrates that, even in the best hands, adverse events can occur and technique education is vital to reduce their incidence. In my opinion, the current "Botox Party" concept exemplifies how medicine should not be practiced.

In this issue of the ARCHIVES, an experienced group of botulinum toxin authors² and injectors present a timely article on "how not to inject."

What is so different about the injection of cosmetic botulinum toxin from other injections? Simply stated, neurotoxin injections are a surgical procedure—because the results depend entirely on the injector's knowledge of the underlying muscular anatomy and pharmacology as well as the principles of aesthetics. Most injections of other medications do not create changes in appearance. Each individual's facial anatomy is unique, as is the way they use the muscles of facial expression.³ In addition, the injecting physician and the subject must share an appreciation of what constitutes desirable, undesirable, or even completely unacceptable outcomes.⁴ A medical patient may accept that his psoriasis never completely goes away, but a cosmetic patient expects a perfect result every time. The bar in cosmesis is thus higher because of the higher expectations of the patients.⁵

Aesthetic physicians have recognized the clinical efficacy and safety of botulinum toxin A as both a primary and an adjunctive treatment to refine and maintain the aesthetic result achievable with other primary treatments such as ablative and nonablative laser resurfacing and soft tissue augmentation. According to the American Society of Aesthetic Plastic Surgery Web site for 2002, there has been a 2356% increase in aesthetic botulinum toxin A treatments since 1997.⁶

Laser resurfacing, whether ablative or nonablative, can only treat the fabric of the skin, and not the underlying facial mimetic musculature. Botulinum toxin treatments thus both enhance and preserve the laser result, and the combination is thus much more effective in facial rejuvenation in the short- and long-term.^{7 - 9} In surgical procedures such as brow-lift and face-lift, the repeated action of the brow and facial depressor musculature can destroy an initially favorable result. Cotreatment of the depressor musculature with botulinum toxin a week or so before the surgical intervention and subsequent postsurgical maintenance therapy can allow the tissues to rest easily in their new elevated position. Research on the stability of brow-lift has shown that it takes approximately 3 months to have the tissues heal onto the new position.¹⁰ Also, about 40% of endoscopic brow-lifts come down somewhat postoperatively in the following 1 to 2 years and this trend can be reversed with botulinum toxin A maintenance treatment.¹¹

Eighty percent of middle-aged women have one brow 1 to 2 mm higher than the other, possibly in part due to preference for sleeping on one side.¹² In aesthetic blepharoplasty, the goal is to remove appropriate amounts of upper eyelid skin to achieve symmetry in the final appearance. If the brow on the lower side is elevated preoperatively with botulinum toxin, symmetrical results are the rule and prevent inadvertent resection of excessive skin (of pseudoexcessive dermatochalasis) on the side of the lower brow.¹³

Perhaps the greatest aesthetic synergy though is achieved with the teamwork of botulinum toxin and soft tissue filling agents. In the glabella, deep resting lines treated with botulinum toxin alone give a very disappointing result at rest because the deep grooves are still present although the individual cannot actively frown. This leads to the perception that the botulinum toxin "didn't work" and to the patient becoming discouraged with botulinum toxin as a therapeutic remedy. I have studied the combined use of 2 hyaluronans in the glabella synchronous with botulinum toxin and have demonstrated the superiority of the combination over either modality alone.¹⁴

In the perioral area, the loss of maxillary and mandibular bone, subcutaneous fat, and dermal collagen and elastin result in a vertical displacement of the mouth so that the corners turn down ("mouth frown"), the vermilion lip narrows, the melolabial and melomental folds deepen, and the individual's facial expression appears bitter and negative. The repeated pursing action of the orbicularis oris in combination with the use of depressor anguli oris and the mentalis exaggerates this appearance. Botulinum toxin chemodenervation of the depressor anguli oris lifts the mouth corners by allowing the opposing muscle zygomaticus major to take up the slack and elevate the mouth corners¹⁵ ; botulinum toxin A treatment of the mentalis softens the associated apple dumpling chin. Synchronous soft tissue augmentation of the deep resting melolabial and melomental folds as well as restoration of the profile of the vermilion lip with soft tissue augmenting agents such as the collagens Zyplast and Zyderm I, which are currently approved by the FDA, give a very pleasing result. In Canada, we have had the hyaluronans approved for several years and we find that Hylaform Plus, Restylane, Perlane, and the fine-line hyaluronans are very convenient because no skin test is required before use. We have used Artecoll in the melolabial and melomental folds and in some vermilion lips. Many of these agents have been thoroughly studied in clinical trials in the United States and are under current review by the FDA.

In summary, there is a great need for detailed background knowledge of the musculofascial and bony anatomy of the regions to be injected. In addition, the injecting physician must understand the pharmacology of the treating agent, BOTOX, as well as having an artistic appreciation of what is currently beautiful in popular culture¹⁶ and understanding the beauty requirements of the individual.¹⁷ Alam et al² have done the cosmetic world a great service by highlighting areas of potential difficulty—now let us hope that all new injecting physicians read and take heed of the suggestions in this article. Let us hope, too, that new injectors are indeed trained physicians, as life-threatening emergencies can occur after cosmetic treatments as well as any other time and it behooves the injector to be able to recognize such events as myasthenic crisis.¹⁸

Chemodenervation is not "just an injection": it is a combination of medicine, pharmacology, surgery, and art.