Keywords
NeurotoxinHyperhidrosisPalmar hyperhidrosisSweatingGlabellar linesCrow’s feetBoNT/AOff-labelHeadacheNeurotoxin usesNovel neurotoxin usesScarsAcneOily skin14.1 Hyperhidrosis
Excessive underarm sweating (axillary hyperhidrosis) is an approved indication for onabotulinumtoxinA (Botox) and has been a welcome addition to the group of conditions treated with BoNT/A. Axillary hyperhidrosis (AH) is an embarrassing condition for affected patients and consists of an over production of sweat beyond what is necessary to keep the body cool. Approximately 3–5% of people in the USA experience this bothersome condition (Rosen and Stewart 2018). Axillary hyperhidrosis usually becomes apparent before age 25, but typically those who suffer with palmar hyperhidrosis usually notice excessive palmar sweating prior to puberty (Rzany et al. 2018).
In addition to BoNT/A, there are several approaches used to help control AH including topical application of aluminum chloride products, radiofrequency or ultrasound treatments, and, in intractable cases, surgical intervention (Rzany et al. 2018). BoNT/A treatment is reserved for patients who fail the more conservative treatments such as antiperspirants.
The typical BoNT/A treatment for axillary hyperhidrosis consists of 15–20 subdermal or subcutaneous injection sites per axilla of 2 units onabotulinumtoxinA or 5u abobotulinumtoxinA (Rosen and Stewart 2018; Rzany et al. 2018; Pirazzini et al. 2017). Pain control at injection sites includes ice or topical anesthetic cream applied 30 min prior to treatment. The duration of the effect of BoNT/A in the axillae tends to be longer than intramuscular injection of the facial muscles , lasting about 6–9 months (Rzany et al. 2018). The longer duration is likely due to the unrealized stimulation by the sympathetic division of the autonomic nervous system on the sweat glands, since acetylcholine acts as neurotransmitter between nerve endings and sweat glands (Rzany et al. 2018; Pirazzini et al. 2017).
Palmar hyperhidrosis can also be treated with BoNT/A successfully when topical hyperhidrosis remedies fail, however, studies are limited and this is an off-label indication (Rzany et al. 2018). Treatment of palmar hyperhidrosis can be a painful procedure and topical anesthetic is usually warranted. Injection of BoNT/A is well tolerated and may improve quality of life in people who suffer with hyperhidrosis of the axillae and palms (Wade et al. 2018).
14.2 Emerging Features of Botulinum Toxins
Faster onset of BoNT/A is an often desired effect when patients are being treated aesthetically. Researchers are working with different strains and subtypes of BoNT/A but ongoing research is necessary to achieve a shorter standardized onset than the current 2–7 days (Allergan 2017; Ipsen Biopharm Ltd 2017; Merz 2018). Novel experimental studies have demonstrated immediate onset of BoNT/A effects when it is reconstituted with lidocaine and epinephrine; however, this technique has not become integrated into aesthetic practice to date (Gassner and Sherris 2000).
Transdermal application of BoNT/A is a novel delivery system that is being studied for a variety of applications (Fonfria et al. 2018). Topically applied BoNT/A could be useful in aesthetics, pain control, and hyperhidrosis, especially in needle-phobic patients. While there was initial enthusiasm for a topical application for BoNT/A to treat hyperhidrosis and lateral canthal lines, as with the pharmacologic gel preparation RT001 (Revance Therapeutics Inc.), the trials were discontinued due to the lack of efficacy in study subjects (Fonfria et al. 2018; Schlessinger et al. 2017). Regardless, topical options are an exciting possibility and further research may ultimately yield an effective transdermal BoNT/A for cosmetic treatment.
Topical BoNT/A preparation would be a welcome option for patients with conditions that require multiple injections in sensitive areas, for example the treatment for axillary or palmar hyperhidrosis. As research progresses, a technical barrier to producing an effective transdermal preparation has emerged. Because of the physical properties of the skin, an enhancer is necessary to carry the BoNT/A across the dermal barrier to become effective (Fonfria et al. 2018). Development of a transdermal type of BoNT/A is currently underway, but there are no results reported to date (Fonfria et al. 2018).
Another version of BoNT, serotype E (BoNT/E), is currently being investigated and is demonstrating a shorter duration of action (Fonfria et al. 2018). Current clinical trials demonstrating safe and effective use of BoNT/E have yielded positive responses in musculoskeletal pain and in elective breast augmentation procedures (Fonfria et al. 2018). Because BoNT/E a shorter acting strain, lasting about 3–6 weeks, it might be useful as an adjunct in pain control and for other therapeutic uses, including seizures (Fonfria et al. 2018).
14.3 Acne
Acne is a common and often embarrassing disease. Treatments include topical and oral medications, acne washes, light-based treatments, and peels (Habif 2016). A novel use for intradermal BoNT/A as an additional acne treatment has emerged and is currently being investigated (Li et al. 2013; Shuo et al. 2019).
Acne lesions form in the pilosebaceous unit and are influenced by hormones that lead to increased sebum production (Habif 2016). Increased sebum production leads to acne lesions and flares in susceptible individuals. Additionally, pore size has also been associated with sebum production (Habif 2016; Shuo et al. 2019). Sebum production in human skin is increased through acetylcholine signaling, therefore because BoNT/A blocks acetylcholine, sebum production is decreased (Li et al. 2013). Literature supports that individuals with oily skin are more responsive to acetylcholine than those with normal skin because the concentration of acetylcholine receptors is higher in their sebaceous glands (Li et al. 2013). This is why botulinum toxin intradermal injections significantly decrease sebum production in oily skin but not in those with normal skin (Li et al. 2013; Shuo et al. 2019).
Oily skin, large pores, and acne lesions are problematic for many people. Pore size was also found to be decreased by the effects of BoNT/A injections and this can have a positive impact on the appearance of the skin (Li et al. 2013; Shuo et al. 2019). Options to alleviate skin and acne concerns are increasing with the advancement of new uses. The advent of intradermal BoNT/A injections offers an exciting new possibility for the treatment of acne (Schlessinger et al. 2017; Shuo et al. 2019). For more information on acne, see Chap. 9.
14.4 Facial Scars
Scarring is a concern for many people who undergo surgical procedures or closure of traumatic wounds on the face (Sherris and Gassner 2002; Goodman 2010). Facial wounds and incisions can leave unsightly scars, especially in areas where muscle movement is frequent. BoNT/A relaxes muscles; therefore, it is postulated that the use of BoNT/A before, during, or after facial surgical procedures would decrease the tension on the closed edges of the incision and result in an improved cosmetic appearance (Sherris and Gassner 2002; Ziade et al. 2013; Gassner et al. 2000).
Therapeutic uses for botulinum neurotoxin
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