Botulinum Toxin for New Indications

  • Doris HexselEmail author
  • Patricia Caspary
  • Carolina Siega
Living reference work entry

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Part of the Clinical Approaches and Procedures in Cosmetic Dermatology book series (CAPCD)


Since it was first approved by FDA for the treatment of glabellar frown lines, botulinum toxin rapidly became one of the most popular cosmetic procedures. In the last decade, its use has increased with improved techniques and new indications in the medical and cosmetic field. These include the treatment of asymmetries, muscles hypertrophy, and different conditions aggravated by sweating, keloids, and some diseases, as depression, rosacea, oily skin and associated conditions, and Raynaud’s phenomenon. Besides its effects in different conditions, new uses might be developed in the future.


Botulinum toxin Rejuvenation Natural look Asymmetries Hailey-Hailey disease Inverse psoriasis Depression Rosacea Sebum Oily skin Hypertrophic scars Keloid Cicatrization Raynaud’s phenomenon 


  1. Alam M, Barrett KC, Hodapp RM, Arndt KA. Botulinum toxin and the facial feedback hypothesis: can looking better make you feel happier? J Am Acad Dermatol. 2008;58:1061–72. Scholar
  2. Ascher B, Talarico S, Cassuto D, Escobar S, Hexsel D, Jaén P, et al. International consensus recommendation on the aesthetic usage of botulinum toxin type A (Speywood unit)-part one: upper facial wrinkles. J Eur Acad Dermatol Venereol. 2010;24(11):1278–84. Scholar
  3. Bartoli D, Battisti A, Cassoni A, Terenzi V, Della Monaca M, Pagnoni M, et al. Contralateral botulinum injections in patients with residual facial asymmetry and contralateral hyperkinesis after primary facial palsy surgery. Ann Ital Chir. 2015;86(3):201–6.PubMedGoogle Scholar
  4. Benedetto AV. Asymmetrical smiles corrected by botulinum toxin serotype A. Dermatol Surg. 2007;33(1 Spec No):S32–6. Scholar
  5. Bessa GR, Grazziotin TC, Manzoni AP, Weber MP, Bonamigo RR. Hailey-Hailey disease treatment with botulinum toxin type A. An Bras Dermatol. 2010;85(5):717–22.PubMedGoogle Scholar
  6. Bhattacharjee K, Singh M, Bhattacharjee H. Extended effect after a single dose of type A botulinum toxin for asymmetric masseter muscle hypertrophy. Indian J Plast Surg. 2015;48(2):196–9. Scholar
  7. Bloom BS, Payongayong L, Mourin A, Goldberg DJ. Impact of intradermal abobotulinumtoxinA on facial erythema of rosacea. Dermatol Surg. 2015;41 Suppl 1:S9–16. Scholar
  8. Carruthers JD, Carruthers JA. Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol. 1992;18(1):17–21.PubMedGoogle Scholar
  9. 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(3):355–66.PubMedGoogle Scholar
  10. Carruthers JD, Glogau RG, Blitzer A. Advances in facial rejuvenation: botulinum toxin type A, hyaluronic acid dermal fillers, and combination therapies-consensus recommendations. Plast Reconstr Surg. 2008;121(5 Suppl):5S–30. Scholar
  11. Carruthers A, Carruthers J, Monheit G, Davis P, Tardie G. Multicenter, randomized, parallel-group study of the safety and effectiveness of onabotulinumtoxinA and hyaluronic acid dermal fillers (24-mg/mL smooth, cohesive gel) alone and in combination for lower facial rejuvenation. Dermatol Surg. 2010;36:2121–34. Scholar
  12. Cha YR, Kim YG, Kim JH, Kim ST. Effect of unilateral injection of botulinum toxin on lower facial asymmetry as evaluated using three-dimensional laser scanning. Dermatol Surg. 2013;39(6):900–6. Scholar
  13. Chang CS, Wallace CG, Hsiao YC, Chang CJ, Chen PK. Botulinum toxin to improve results in cleft lip repair: a double-blinded, randomized, vehicle-controlled clinical trial. PLoS One. 2014;9(12), e115690. eCollection 2014.PubMedPubMedCentralGoogle Scholar
  14. Chiaravalloti A, Payette M. Hailey-Hailey disease and review of management. J Drugs Dermatol. 2014;13(10):1254–7.PubMedGoogle Scholar
  15. Coleman KR, Carruthers J. Combination therapy with BOTOX and fillers: the new rejuvenation paradigm. Dermatol Ther. 2006;19(3):177–88. Scholar
  16. Davis SA, Feldman SR, McMichael AJ. Management of keloids in the United States, 1990–2009: an analysis of the National Ambulatory Medical Care Survey. Dermatol Surg. 2013;39(7):988–94. Scholar
  17. Dayan SH, Ashourian N. Considerations for achieving a natural face in cosmetic procedures. JAMA Facial Plast Surg. 2015;17(6):395. Scholar
  18. Dayan SH, Pritzker RN, Arkins JP. A new treatment regimen for rosacea: onabotulinumtoxinA. J Drugs Dermatol. 2012;11(12):e76–9.PubMedGoogle Scholar
  19. de Maio M. Ethnic and gender considerations in the use of facial injectables: male patients. Plast Reconstr Surg. 2015;136(5 Suppl):40S–3. Scholar
  20. Fedorowicz Z, van Zuuren EJ, Schoones J. Botulinum toxin for masseter hypertrohphy. Cochrane Database Syst Rev. 2013;9:CD007510. Scholar
  21. Finzi E, Rosenthal NE. Treatment of depression with onabotulinumtoxinA: a randomized, double-blind, placebo controlled trial. J Psychiatr Res. 2014;52:1–6. Scholar
  22. Finzi E, Wasserman E. Treatment of depression with botulinum toxin A: a case series. Dermatol Surg. 2006;32(5):645–9; discussion 649–50. Scholar
  23. Fregene A, Ditmars D, Siddiqui A. Botulinum toxin type A: a treatment option for digital ischemia in patients with Raynaud’s phenomenon. J Hand Surg [Am]. 2009;34(3):446–52. Scholar
  24. Gassia V, Raspaldo H, Niforos FR, Michaud T. Global 3-dimensional approach to natural rejuvenation: recommendations for perioral, nose, and ear rejuvenation. J Cosmet Dermatol. 2013;12(2):123–36. Scholar
  25. Gassner HG, Brissett AE, Otley CC, Boahene DK, Boggust AJ, Weaver AL, et al. Botulinum toxin to improve facial wound healing: a prospective, blinded, placebo-controlled study. Mayo Clin Proc. 2006;81(8):1023–8. Scholar
  26. Gauglitz GG, Bureik D, Dombrowski Y, Pavicic T, Ruzicka T, Schauber J. Botulinum toxin A for the treatment of keloids. Skin Pharmacol Physiol. 2012;25(6):313–8. Scholar
  27. Haubner F, Ohmann E, Müller-Vogt U, Kummer P, Strutz J, Gassner HG. Effects of botulinum toxin a on cytokine synthesis in a cell culture model of cutaneous scarring. Arch Facial Plast Surg. 2012;14(2):122–6. Scholar
  28. Haubner F, Leyh M, Ohmann E, Sadick H, Gassner HG. Effects of botulinum toxin A on patient-specific keloid fibroblasts in vitro. Laryngoscope. 2014;124(6):1344–51. Scholar
  29. Heckmann M, Teichmann B, Schröder U, Sprengelmeyer R, Ceballos-Baumann AO. Pharmacologic denervation of frown muscles enhances baseline expression of happiness and decreases baseline expression of anger, sadness, and fear. J Am Acad Dermatol. 2003;49(2):213–6. Scholar
  30. Hexsel D. Combining procedures with botulinum toxin in dermatology and dermatological surgery. In: Hexsel D, Almeida AT, editors. Cosmetic use of botulinum toxin. São Paulo: AGE; 2002. p. 211–5.Google Scholar
  31. Hexsel D, Brum C, Siega C, Schilling-Souza J, Dal’Forno T, Heckmann M, et al. Evaluation of self-esteem and depression symptoms in depressed and nondepressed subjects treated with onabotulinumtoxinA for glabellar lines. Dermatol Surg. 2013;39(7):1088–96. Scholar
  32. Ho D, Jagdeo J. Successful botulinum toxin (onabotulinumtoxinA) treatment of Hailey-Hailey disease. J Drugs Dermatol. 2015;14(1):68–70.PubMedGoogle Scholar
  33. Hohl D, Mauro T, Görög JP. Genodermatoses: Darier’s disease and Hailey-Hailey disease. In: Bolognia JL, Jorizzo JL, Rapini R, editors. Dermatology. vol. I. Edinburgh: Mosby; 2003. p. 823–33.Google Scholar
  34. Iorio ML, Masden DL, Higgins JP. Botulinum toxin A treatment of Raynaud’s phenomenon: a review. Semin Arthritis Rheum. 2012;41(4):599–603. Scholar
  35. Iozzo I, Tengattini V, Antonucci VA. Multipoint and multilevel injection technique of botulinum toxin A in facial aesthetics. J Cosmet Dermatol. 2014;13(2):135–42. Scholar
  36. Jeong HS, Lee BH, Sung HM, Park SY, Ahn DK, Jung MS, et al. Effect of Botulinum toxin type A on differentiation of fibroblasts derived from scar tissue. Plast Reconstr Surg. 2015;136(2):171e–8. Scholar
  37. Katon WJ. Epidemiology and treatment of depression in patients with chronic medical illness. Dialogues Clin Neurosci. 2011;13:7–23.PubMedGoogle Scholar
  38. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, et al. National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289(23):3095–105. Scholar
  39. Khan TT, Herne K, Dayan SH, Woodward JA. Facial blanching due to neurotoxins: proposed mechanisms. Dermatol Surg. 2013;39(1 Pt 1):24–9. Scholar
  40. Kim YS, Lee HJ, Cho S, Lee JD, Kim HS. Early postoperative treatment of thyroidectomy scars using botulinum toxin: a split-scar, double-blind randomized controlled trial. Wound Repair Regen. 2014;22(5):605–12. Scholar
  41. Klein FH, Brenner FM, Sato MS, Robert FM, Helmer KA. Lower facial remodeling with botulinum toxin type A for the treatment of masseter hypertrophy. An Bras Dermatol. 2014;89(6):878–84. Scholar
  42. Koeyers WJ, Van Der Geer S, Krekels G. Botulinum toxin type A as an adjuvant treatment modality for extensive Hailey-Hailey disease. J Dermatolog Treat. 2008;19(4):251–4. Scholar
  43. Kruger TH, Wollmer MA. Depression – an emerging indication for botulinum toxin treatment. Toxicon. 2015; pii: S0041-0101(15)30094-5. Scholar
  44. Landau M. Combination of chemical peelings with botulinum toxin injections and dermal fillers. J Cosmet Dermatol. 2006;5(2):121–6. Scholar
  45. Lapiere JC, Hirsh A, Gordon KB, Cook B, Montalvo A. Botulinum toxin type A for the treatment of axillary Hailey-Hailey disease. Dermatol Surg. 2000;26(4):371–4.PubMedGoogle Scholar
  46. Lee DH, Jin SP, Cho S, Feneran A, Youn CS, Won CH, et al. RimabotulinumtoxinB versus onabotulinumtoxinA in the treatment of masseter hypertrophy: a 24-week double-blind randomized split-face study. Dermatology. 2013;226(3):227–32. Scholar
  47. Lewis MB, Bowler PJ. Botulinum toxin cosmetic therapy correlates with a more positive mood. Cosmet Dermatol. 2009;8(1):24–6. Scholar
  48. Li ZJ, Park SB, Sohn KC, Lee Y, Seo YJ, Kim CD, et al. Regulation of lipid production by acetylcholine signalling in human sebaceous glands. J Dermatol Sci. 2013;72(2):116–22. Scholar
  49. López-Ferrer A, Alomar A. Botulinum toxin A for the treatment of familial benign pemphigus. Actas Dermosifiliogr. 2012;103(6):532–5. Scholar
  50. Magid M, Reichenberg JS, Poth PE, Robertson HT, LaViolette AK, Kruger TH, et al. Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014;75(8):837–44. Scholar
  51. Min P, Xi W, Grassetti L, Trisliana Perdanasari A, Torresetti M, Feng S, et al. Sebum production alteration after Botulinum toxin type A injections for the treatment of forehead rhytides: a prospective randomized double-blind dose-comparative clinical investigation. Aesthet Surg J. 2015;35(5):600–10. Scholar
  52. Motegi SI, Yamada K, Toki S, Uchiyama A, Kubota Y, Nakamura T, Ishikawa O. Beneficial effect of botulinum toxin A on Raynaud’s phenomenon in Japanese patients with systemic sclerosis: a prospective, case series study. J Dermatol. 2015. Scholar
  53. Neumeister MW. Botulinum toxin type A in the treatment of Raynaud’s phenomenon. J Hand Surg [Am]. 2010;35(12):2085–92. Scholar
  54. Oh YJ, Lee NY, Suh DH, Koh JS, Lee SJ, Shin MK. A split-face study using botulinum toxin type B to decrease facial erythema index. J Cosmet Laser Ther. 2011;13(5):243–8. Scholar
  55. Park KY, Hyun MY, Jeong SY, Kim BJ, Kim MN, Hong CK. Botulinum toxin for the treatment of refractory erythema and flushing of rosacea. Dermatology. 2015;230:299–301. Scholar
  56. Prodromidou A, Frountzas M, Vlachos DE, Vlachos GD, Bakoyiannis I, Perrea D, et al. Botulinum toxin for the prevention and healing of wound scars: a systematic review of the literature. Plast Surg (Oakv). 2015;23(4):260–4.Google Scholar
  57. Raspaldo H, Niforos FR, Gassia V, Dallara JM, Bellity P, Baspeyras M, et al. Lower-face and neck antiaging treatment and prevention using onabotulinumtoxin A: the 2010 multidisciplinary French consensus – part 2. J Cosmet Dermatol. 2011;10(2):131–49. Scholar
  58. Rose AE, Goldberg DJ. Safety and efficacy of intradermal injection of botulinum toxin for the treatment of oily skin. Dermatol Surg. 2013;39(3 Pt 1):443–8. Scholar
  59. Saber M, Brassard D, Benohanian A. Inverse psoriasis and hyperhidrosis of the axillae responding to botulinum toxin type A. Arch Dermatol. 2011;147(5):629–30. Scholar
  60. Sadiq SA, Khwaja S, Saeed SR. Botulinum toxin to improve lower facial symmetry in facial nerve palsy. Eye(Lond). 2012;26(11):1431–6. Scholar
  61. Semchyshyn NL, Kilmer SL. Does laser inactivate botulinum toxin? Dermatol Surg. 2005;31(4):399–404.PubMedGoogle Scholar
  62. Serri J, Legré R, Veit V, Guardia C, Gay AM. Botulinum toxin type A contribution in the treatment of Raynaud’s phenomenon due to systemic sclerosis. Ann Chir Plast Esthet. 2013;58(6):658–62. Scholar
  63. Shaarawy E, Hegazy RA, Abdel Hay RM. Intralesional botulinum toxin type A equally effective and better tolerated than intralesional steroid in the treatment of keloids: a randomized controlled trial. J Cosmet Dermatol. 2015;14(2):161–6. Scholar
  64. Shah AR. Use of intradermal botulinum toxin to reduce sebum production and facial pore size. J Drugs Dermatol. 2008;7(9):847–50.PubMedGoogle Scholar
  65. Steinsapir KD, Rootman D, Wulc A, Hwang C. Cosmetic microdroplet Botulinum toxin A forehead lift: a new treatment paradigm. Ophthal Plast Reconstr Surg. 2015;31(4):263–8. Scholar
  66. Sterodimas A, Nicolaou M, Paes TR. Successful use of Botulinum toxin-A for the treatment of neck and anterior chest wall flushing. Clin Exp Dermatol. 2003;28(6):592–4.PubMedGoogle Scholar
  67. Tiryaki T, Ciloglu NS. Eyebrow asymmetry: definition and symmetrical correction using botulinum toxin A. Aesthet Surg J. 2007;27(5):513–7. Scholar
  68. Tollefson TT, Senders CM, Sykes JM, Byorth PJ. Botulinum toxin to improve results in cleft lip repair. Arch Facial Plast Surg. 2006;8(3):221–2. Scholar
  69. Uppal L, Dhaliwal K, Butler PE. A prospective study of the use of botulinum toxin injections in the treatment of Raynaud’s syndrome associated with scleroderma. J Hand Surg Eur Vol. 2014;39(8):876–80. Scholar
  70. Van de Kerkhof. Psoriasis. In: Bolognia JL, Jorizzo JL, Rapini R, editors. Dermatology. vol. I. Edinburgh: Mosby; 2003. p. 125–49.Google Scholar
  71. Walling HW. Primary hyperhidrosis increases the risk of cutaneous infection: a case–control study of 387 patients. J Am Acad Dermatol. 2009;61(2):242–6. Scholar
  72. Wang G, Li C, Gao T, Liu Y. Clinical analysis of 48 cases of inverse psoriasis: a hospital-based study. Eur J Dermatol. 2005;15(3):176–8.PubMedGoogle Scholar
  73. Weinkle AP, Doktor V, Emer J. Update on the management of rosacea. Clin Cosmet Investig Dermatol. 2015;8:159–77. eCollection 2015.PubMedPubMedCentralGoogle Scholar
  74. Wilkin J, Dahl M, Detmar M, Drake L, Liang MH, Odom R, Powell F, National Rosacea Society Expert Committee. Standard grading system for rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2004;50(6):907–12. Scholar
  75. Williams DR, González HM, Neighbors H, Nesse R, Abelson JM, Sweetman J, et al. Prevalence and distribution of major depressive disorder in African Americans, Caribbean blacks, and non-Hispanic whites: results from the national survey of American life. Arch Gen Psychiatry. 2007;64(3):305–15. Scholar
  76. Wollmer MA, de Boer C, Kalak N, Beck J, Götz T, Schmidt T, et al. Facing depression with botulinum toxin: a randomized controlled trial. J Psychiatr Res. 2012;46(5):574–81. Scholar
  77. WT W. Microbotox of the lower face and neck: evolution of a personal technique and its clinical effects. Plast Reconstr Surg. 2015;136(5 Suppl):92S–100. Scholar
  78. Xiao Z, Zhang F, Cui Z. Treatment of hypertrophic scars with intralesional botulinum toxin type A injections: a preliminary report. Aesthetic Plast Surg. 2009;33(3):409–12. Scholar
  79. Xiao Z, Zhang F, Lin W, Zhang M, Liu Y. Effect of botulinum toxin type A on transforming growth factor beta1 in fibroblasts derived from hypertrophic scar: a preliminary report. Aesthetic Plast Surg. 2010;34(4):424–7. Scholar
  80. Xiao Z, Zhang M, Liu Y, Ren L. Botulinum toxin type a inhibits connective tissue growth factor expression in fibroblasts derived from hypertrophic scar. Aesthetic Plast Surg. 2011;35(5):802–7. Scholar
  81. Xiaoxue W, Xi C, Zhibo X. Effects of botulinum toxin type A on expression of genes in keloid fibroblasts. Aesthet Surg J. 2014;34(1):154–9. Scholar
  82. Yuraitis M, Jacob CI. Botulinum toxin for the treatment of facial flushing. Dermatol Surg. 2004;30(1):102–4.PubMedGoogle Scholar
  83. Zanchi M, Favot F, Bizzarini M, Piai M, Donini M, Sedona P. Botulinum toxin type-A for the treatment of inverse psoriasis. J Eur Acad Dermatol Venereol. 2008;22(4):431–6. Scholar
  84. Zhang X, Hu Y, Nie Z, Song Y, Pan Y, Liu Y, Jin L. Treatment of Raynaud’s phenomenon with botulinum toxin type A. Neurol Sci. 2015;36(7):1225–31. Scholar
  85. Zhao H, Lian Y. Clinical and image improvement of Raynaud’s phenomenon after botulinum toxin type A treatment. Australas J Dermatol. 2015;56(3):202–5. Scholar
  86. Zhibo X, Miaobo ZJ. Botulinum toxin type A affects cell cycle distribution of fibroblasts derived from hypertrophic scar. J Plast Reconstr Aesthet Surg. 2008;61(9):1128–9. Scholar
  87. Ziade M, Domergue S, Batifol D, Jreige R, Sebbane M, Goudot P, et al. Use of botulinum toxin type A to improve treatment of facial wounds: a prospective randomised study. J Plast Reconstr Aesthet Surg. 2013;66(2):209–14. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Doris Hexsel
    • 1
    • 2
    Email author
  • Patricia Caspary
    • 3
  • Carolina Siega
    • 3
  1. 1.Department of DermatologyBrazilian Center for Studies in DermatologyPorto Alegre / Rio de JaneiroBrazil
  2. 2.Hexsel Dermatology ClinicPorto AlegreBrazil
  3. 3.Brazilian Center for Studies in DermatologyPorto AlegreBrazil

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