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Botulinum toxin related research in maxillofacial plastic and reconstructive surgery

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EDITORIAL Open Access

Botulinum toxin related research in maxillofacial plastic and reconstructive surgery

Tae-Geon Kwon

Botulism caused by food poisoning was characterized by mydriasis and skeletal muscle paralysis, which was first described by Justinus Kerner in 1820 [1]. The cause of botulism was botulinum neurotoxin produced by anaer- obic, spore-forming bacteria of the genus Clostridium [2]. Botulinum toxin (BTX) became to be the first med- ically applied toxin. The first clinical use of BTX was re- ported concerning the treatment of strabismus in ophthalmologic field in 1980 [3]. Nine years later, the Food and Drug Administration (FDA) approved the clin- ical application of BTX for adult strabismus and bleph- arospasm [4]. BTX inhibits acetylcholine exocytosis at neuromuscular junction of the preganglionic sympa- thetic/parasympathetic nerve fibers and postganglionic parasympathetic nerves [5].

BTX is clinically administrated to treat various thera- peutic indications: strabismus, migraine, bladder dys- tonia, hyperhidrosis, cervical dystonia, upper limb spasticity, voice abnormality, chronic pain management, and cerebral palsy [6]. Recently, the most popular indi- cation in public is the control of facial wrinkle [7]. In oral and maxillofacial surgery field, BTX injection is ap- plied not only for cosmetic purposes such as glabella line correction, platysma band correction, or gummy smile but also for therapeutic indications such as masseteric or temporalis muscle hypertrophy [8–10], temporoman- dibular joint disorders [9, 11], salivary gland secretory disorders (including sialorrhea, Frey syndrome) [12], hypertrophic scars [13], facial pains [14], and facial par- alysis [15, 16]. Especially in dental field, it had been re- ported that BTX improved painful symptoms as high as 90 % of temporomandibular joint disorders related to masticatory muscles [17]. In cosmetic purpose in dental field, excessive gingival exposure during smile or

asymmetric smile can be corrected by the BTX injection into peri-oral muscles [18, 19]. Therefore, even though BTX treatment had been historically dermatologists and neurologists’ jurisdiction, it now became the dentists’

jurisdiction because the training and scientific know- ledge covers the entire head and neck region [19].

However, there are a number of complications associ- ated with the BTX injection especially related with the accidental overdose. According to the previous report, there are various local and systemic side effects after BTX injection. Pain, edema, headache, and bruising would be the common loco-regional side effects, and nausea, fatigue, headache, facial pain, flu-like symptoms, anxiety, and itching can appear as systemic side effects after BTX administration [1, 20]. In 2005, it was re- ported that the adverse event reported to the FDA (Dec 1989~May 2003) after therapeutic and cosmetic use of BTX was 1437 cases. Among these, 217 serious adverse events were reported including 28 reported deaths; re- spiratory arrest (n = 6), myocardial infarction (n = 5), cerebrovascular accident (n = 3), pulmonary embolism (n = 2), and others (n = 3) [21]. All of them were related to therapeutic application rather than cosmetic purpose of the BTX.

Even though there are numerous publications report- ing successful outcomes after BTX application, there are only a few scientific reports with high level of scientific evidence. Because the clinical research had not been car- ried out with randomized, controlled, blinded settings, more clinical and experimental research should be en- couraged. Clinical research need to be carried out more tightly under controlled condition with a prospective, randomized design rather than demonstration of suc- cessful case series. At the same time, to overcome funda- mental limitations of the BTX, the basic research is needed to advance and improve the clinical application of BTX.

Correspondence:kwondk@knu.ac.kr

Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University, 2177 Dalgubeoldaero, Jung Gu, Daegu 41940, South Korea

Maxillofacial Plastic and Reconstructive Surgery

© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Kwon Maxillofacial Plastic and Reconstructive Surgery (2016) 38:34 DOI 10.1186/s40902-016-0080-2

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Competing interests

The author declares that he has no competing interests.

Received: 20 August 2016 Accepted: 20 August 2016

References

1. Lu DW, Lippitz J (2009) Complications of botulinum neurotoxin. Dis Mon 55:198–211

2. Popoff MR, Bouvet P (2013) Genetic characteristics of toxigenic Clostridia and toxin gene evolution. Toxicon 75:63–89

3. Scott AB (1980) Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology 87:1044–1049 4. Scott AB (2004) Development of botulinum toxin therapy. Dermatol Clin 22:

131–133

5. Khanna S, Jain S (2006) Botox: the poison that heals. Int Dent J 56:356–358 6. de Maio M (2008) Therapeutic uses of botulinum toxin: from facial palsy to

autonomic disorders. Expert Opin Biol Ther 8:791–798

7. Jaspers GW, Pijpe J, Jansma J (2011) The use of botulinum toxin type A in cosmetic facial procedures. Int J Oral Maxillofac Surg 40:127–133 8. Ihde SK, Konstantinovic VS (2007) The therapeutic use of botulinum toxin in

cervical and maxillofacial conditions: an evidence-based review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104:e1–e11

9. Jeong CH, Ryu JY, Lee WY, Kim HM (2015) Simultaneous surgery for subcondylar fracture and prominent angle of the mandible. Maxillofac Plast Reconstr Surg 37:26

10. Lee CJ, Kim SG, Kim YJ, Han JY, Choi SH, Lee SI (2007) Electrophysiologic change and facial contour following botulinum toxin A injection in square faces. Plast Reconstr Surg 120:769–778

11. Kim HS, Yun PY, Kim YK (2016) A clinical evaluation of botulinum toxin-A injections in the temporomandibular disorder treatment. Maxillofac Plast Reconstr Surg 38:5

12. Su JZ, Cai ZG, Yu GY (2015) Microvascular autologous submandibular gland transplantation in severe cases of keratoconjunctivitis sicca. Maxillofac Plast Reconstr Surg 37:5

13. Zhang DZ, Liu XY, Xiao WL, Xu YX (2016) Botulinum toxin type A and the prevention of hypertrophic scars on the maxillofacial area and neck: a meta- analysis of randomized controlled trials. PLoS One 11:e0151627

14. Srivastava S, Kharbanda S, Pal US, Shah V (2015) Applications of botulinum toxin in dentistry: a comprehensive review. Natl J Maxillofac Surg 6:152–159 15. Garcia RM, Hadlock TA, Klebuc MJ, Simpson RL, Zenn MR, Marcus JR.

Contemporary solutions for the treatment of facial nerve paralysis (2015) Plast Reconstr Surg 135:1025e-1046e. doi:10.1097/PRS.0000000000001273.

16. Sinclair CF, Gurey LE, Blitzer A (2013) Oromandibular dystonia: long-term management with botulinum toxin. Laryngoscope 123:3078–3083 17. Bhogal PS, Hutton A, Monaghan A (2006) A review of the current uses of

Botox for dentally-related procedures. Dent Update 33:165–168 18. Niamtu J 3rd (2003) Botulinum toxin A: a review of 1,085 oral and

maxillofacial patient treatments. J Oral Maxillofac Surg 61:317–324 19. Hoque A, McAndrew M (2009) Use of botulinum toxin in dentistry. N Y

State Dent J 75:52–55

20. Archana MS (2016) Toxin yet not toxic: botulinum toxin in dentistry. Saudi Dent J 28:63–69

21. Cote TR, Mohan AK, Polder JA, Walton MK, Braun MM (2005) Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J Am Acad Dermatol 53:

407–415

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