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BTX-A can be used before or after the surgical manipulation to either enhance or sustain benefits If injected in the preoperative period, the toxin may allow improved tissue manipulation and reduced incisional tension leading to improved healing Prior to endoscopic brow lift or a face lift using endoscopy, BTX-A injections help in raising the position of the brow and can reduce the amount of surgical manipulations necessary Finally, when used after surgery, BTX-A weakens the musculature, prolonging the anticipated effect105
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COMBINED THERAPIES: BTX-A AND OTHER REJUVENATION MODALITIES
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The superiority of BTX-A when used with other cosmetic procedures has been documented in a number of studies When administered 1 week prior to the treatment with filling agents, BTX-A prevents the distortion of the fillers and prolongs the effects of augmentation by reducing the muscular activity associated with rhytide formation106 BTX-A therapy works synergistically with resurfacing techniques to provide an optimal improvement of dynamic rhytides and in some cases enhance
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TABLE 22-6 Factors of Proteins That Increase Immunogenicity Foreign instead of endogenous Large rather than small size Denatured rather than native Presence of adjuvants Aggregated rather than unaggregated Quantity present Frequency encountered These properties of toxin preparations make them more likely to cause an antibody response Of course, other factors such as the age and genetics of a patient are also important
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CHAPTER 22 BOTULINUM TOXIN
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FIGURE 22-32 Injection sites on hands are approximately 15 cm apart further injections The use of other serotypes (F or B) may benefit those who have developed antibody resistance There are two types of therapy resistance to BTX, primary and secondary A patient who does not respond to the first injection of BTX-A is referred to as a primary nonresponder, but reasons for nonresponse can include inappropriate site of injection, poor technique, and/or insufficient dose109,110 Immunogenicity should be suspected in a patient who no longer responds to BTX-A ( secondary nonresponder ) following a successful course of earlier injections Antibody formation could be targeted against the neurotoxin component of BTX or against its nontoxic protein component The recommended approach is to inject 20 U BTX into the hypothenar or forehead muscles If the patient responds to BTX, then transient weakness will develop in the muscle 1 to 2 weeks after injection An alternative is to take blood for an antibody assay that is rarely used In secondary nonresponders, the problem can be further overcome by using a different BTX serotype, for example, BTX-B if resistance develops to BTX-A Risk factors for the development of antibodies include higher doses, shorter intervals between injections, booster doses, and young age Recommendations to help prevent development of antibodies include the following: (1) use of the smallest possible dose to achieve relief, (2) an interval between injections of at least 1 month (the preferred interval is 3 months), and (3) touch-up injection avoidance Many researchers have postulated that the risk of antibody formation is due in part to the quantity of protein or the protein load of the toxin, the type of protein present in the toxin, and to other factors listed in Table 22-6 Manufacturers of BTX have attempted to minimize each of these factors in order to create a less immunogenic product For example, the original Botox that was used until December 1997 contained a higher level of protein than the Botox currently in use; therefore, it
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should lead to a lower incidence of antibody formation As previously discussed, Merz Pharmaceuticals, the manufacturer of the new BTX product Xeomin, claims that its product contains a negligible amount of bacterial proteins (06 ng) with lower immune response In spite of the concerns regarding immunogenicity, there are no known or published reports of antibody production in patients treated with doses of any of the available BTX products for cosmetic indications, which may be explained by the lower doses used in comparison with neurologic and cervical dystonia indications where reports of resistance are centered111
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