Skip to main content
SpringerLink
Log in

Managing Adverse Events Associated with Botulinum Toxin Type A

A Focus on Cosmetic Procedures

  • Leading Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Botulinum toxin A (BTXA) has become a widely used drug in cosmetic dermatology, not only to treat focal hyperhidrosis but also hyperkinetic facial lines, platysma bands, décolleté bands, and other skin features. The spectrum of possible adverse effects of BTXA is broad but fortunately those that have been observed with cosmetic use of this product are generally mild and transient. The major tools for preventing adverse effects from BTXA are knowledge and skill. Use of correct injection techniques is mandatory since most unwanted effects are caused by incorrect technique. Knowledge of the target structures, e.g. the facial and extrafacial muscles, allows physicians to select the optimal dose, time and technique. The most common adverse effects are pain and hematoma. In the periocular region, lid and brow ptosis are important adverse effects. Adverse effects such as pain, hematoma, ecchymosis, and bruising may also occur in the upper and lower face and at extrafacial sites. Other possible adverse effects seen in other indications that the user of BTXA in cosmetic dermatology should be wary of include induction headaches and possible interaction with concomitant medications. Induction of neutralizing antibodies due to cosmetic BTXA treatment has not been observed. This article also outlines recommendations regarding use of BTXA. Of these, the most important for avoiding most unwanted adverse effects are the proper techniques of dilution, storage, and injection, as well as the careful exclusion of patients with any contraindications. Pain, hematoma, ecchymosis, and bruising can be prevented by cooling the skin before and after BTXA injection. Upper lid ptosis may be partly corrected using apraclonidine or phenylephrine eyedrops. If simple rules relating to the indications for and application of BTXA are followed, this is a safe and effective drug in cosmetic dermatology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Tchitchikine A. Essai d’immunisation par la voie gastrointestinale contre la toxine botulique [letter]. Ann Just Pasteur. 1905; XIX: 335

    Google Scholar 

  2. Schantz EJ, Johnson EA. Botulinum toxin: the story of its development in human disease. Perspect Biol Med. 1997; 40: 317–27

    PubMed  CAS  Google Scholar 

  3. Brin ME. Botulinum toxin: chemistry, pharmacology, toxicity, and immunology. Muscle Nerve. 1997; 20 Suppl. 6: S146–68

    Article  Google Scholar 

  4. Huang W, Foster JA, Rogachefsky AS. Pharmacology of botulinum toxin. J Am Acad Dermatol. 2000; 43: 249–59

    Article  PubMed  CAS  Google Scholar 

  5. Sampaio C, Ferreira JJ, Simoes F, et al. DYSBOT: a single-blind, randomized parallel study to determine whether any differences can be detected in the efficacy and tolerability of two formulations of botulinum toxin type A: Dysport and Botox: assuming a ratio of 4:1. Mov Disord. 1997; 12: 1013–8

    Article  PubMed  CAS  Google Scholar 

  6. Odergren T, Hjaltason H, Kaakkola S, et al. A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport and Botox in the treatment of cervical dystonia. J Neurol Neurosurg Psychiatry. 1998; 64: 6–12

    Article  PubMed  CAS  Google Scholar 

  7. Ranoux D, Gury C, Fondarai J, et al. Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia. J Neurol Neurosurg Psychiatry. 2002; 72: 459–62

    PubMed  CAS  Google Scholar 

  8. Carruthers A, Carruthers J. Cosmetic use of botulinum A exotoxin. Adv Dermatol. 1997; 12: 325-47

    PubMed  CAS  Google Scholar 

  9. Lowe NJ, Maxwell A, Harper H. Botulinum A exotoxin for glabellar folds: a double-blind, placebo-controlled study with an electromyographic injection technique. J Am Acad Dermatol. 1996; 35: 569–72

    Article  PubMed  CAS  Google Scholar 

  10. Carruthers JA, Lowe NJ, Menter MA, et al. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol. 2002; 46: 840–9

    Article  PubMed  Google Scholar 

  11. Lowe NJ, Lask G, Yamauchi P, et al. Bilateral, double-blind, randomized comparison of 3 doses of botulinum toxin type A and placebo in patients with crow’s feet. J Am Acad Dermatol. 2002; 47: 834–40

    Article  PubMed  Google Scholar 

  12. Matarasso SL. Comparison of botulinum toxin types A and B: a bilateral and double-blind randomized evaluation in the treatment of canthal rhytides. Dermatol Surg. 2003; 29: 7–13

    Article  PubMed  Google Scholar 

  13. Niamtu J. Botulinum toxin A: a review of 1,085 oral and maxillofacial patient treatments. J Oral Maxillofac Surg. 2003; 61: 317–24

    Article  PubMed  Google Scholar 

  14. Wilson F. Botulinum toxin-A risks overcome by proper technique. Cosmetic Surg Times 2001 Mar, 12

    Google Scholar 

  15. Klein AW. Complications and adverse reactions with the use of botulinum toxin. Dis Mon. 2002; 48: 336–56

    Article  PubMed  Google Scholar 

  16. Zechmeister M, De Oliveira Dal’Fomo T. Conservation, dilution and storage after dilution. In: Hexsel D, Trinidade de Almeida A, editors. Cosmetic use of botulinum toxin. Porto Alegre: AGE Editoria, 2002: 43–4

    Google Scholar 

  17. Habbema L. Facial esthetics and patient selection. Clin Dermatol. 2004; 22: 14–7

    Article  PubMed  Google Scholar 

  18. Carruthers A, Carruthers J. Clinical indications and injection technique for the cosmetic use of botulinum A exotoxin. Dermatol Surg. 1998; 24: 1189–94

    Article  PubMed  CAS  Google Scholar 

  19. Matarasso SL. Complications of botulinum A exotoxin for hyperfunctional lines. Dermatol Surg. 1998; 24: 1249–54

    Article  PubMed  CAS  Google Scholar 

  20. Li M, Goldberger BA, Hopkins C. Fatal case of BOTOX (R)-related anaphylaxis? J Forensic Sci. In press

  21. Cohen DE, Kaufmann JM. Hypersensitivity reactions to products and devices in plastic surgery. Facial Plast Surg Clin N Am. 2003; 11: 253–65

    Article  Google Scholar 

  22. Cox NH, Duffey P, Royle J. Fixed drug eruption caused by lactose in an injected botulinum toxin preparation. J Am Acad Dermatol. 1999; 40: 263–4

    Article  PubMed  CAS  Google Scholar 

  23. Taylor SL, Hefle SL. Ingredient and labeling issues associated with allergenic foods. Allergy. 2001; 56 Suppl. 67: 64–9

    Article  PubMed  Google Scholar 

  24. LeWitt PA, Trosch RM. Idiosyncratic reactions to intramuscular botulinum toxin type A injection. Mov Disord. 1997; 12: 1064–7

    Article  PubMed  CAS  Google Scholar 

  25. Claus D, Druschky A, Erbguth F. Botulinum toxin: influence on respiratory heart rate variation. Mov Disord. 1995; 10: 574–9

    Article  PubMed  CAS  Google Scholar 

  26. Malnick SD, Metchnik L, Somin M, et al. Fatal heart block following treatment with botulinum toxin for achalasia. Am J Gastroenterol. 2000; 95: 3333–4

    Article  PubMed  CAS  Google Scholar 

  27. Tsuboi M, Furukawa Y, Kurogouchi F, et al. Botulinum neurotoxin A blocks cholinergic ganglionic neurotransmission in the dog heart. Jpn J Pharmacol. 2002; 89: 249–54

    Article  PubMed  CAS  Google Scholar 

  28. Wollina U. Botulinum A toxin for wrinkles: release from tension headache. J Fur Acad Dermatol Venereol. 2000; 14: 142–3

    Article  CAS  Google Scholar 

  29. Silberstein S, Mathew N, Saper J, et al. Botulinum toxin type A as a safe migraine preventive treatment. Headache. 2000; 40: 445–50

    Article  PubMed  CAS  Google Scholar 

  30. Patel MP, Talmor M, Nolan WB. Botox and collagen for glabellar furrows: advantages of combination therapy. Ann Plast Surg. 2004; 52: 442–7

    Article  PubMed  Google Scholar 

  31. Alam M, Arndt KA, Dover JS. Severe, intractable headache after injection with botulinum A exotoxin: report of 5 cases. J Am Acad Dermatol. 2002; 46: 62–5

    Article  PubMed  Google Scholar 

  32. Goldman A. Botulinum toxin in plastic surgery: experience and indications in 1200 treated areas. Rev Soc Bras Cir Past Sao Paulo. 1999; 14: 21–30

    Google Scholar 

  33. Hexsel D, Mazzuco R, Zechmeister M, et al. Complications and adverse effects: diagnosis and treatment. In: Hexsel D, Trinidade de Almeida A, editors. Cosmetic use of botulinum toxin. Porto Alegre: AGE Editoria, 2002: 233–9

    Google Scholar 

  34. Fiacchino F, Grandi L, Soliveri P, et al. Sensitivity to vecuronium after botulinum toxin administration. J Neurosurg Anesthesiol. 1997; 9: 149–53

    Article  PubMed  CAS  Google Scholar 

  35. Matarasso A, Deva AK, and the American Society of Plastic Surgeons DATA Committee. Botulinum toxin. Plast Reconstr Surg. 2002; 109: 1191–7

    Article  PubMed  Google Scholar 

  36. Letessier S. Treatment of wrinkles with botulinum toxin. J Dermatol Treat. 1999; 10: 31–6

    Article  Google Scholar 

  37. Sunness JS, Kelman S. Cosmetic Botox injection mimicking myasthenia gravis. Plast Reconstr Surg. 2004; 113: 1515

    PubMed  Google Scholar 

  38. Wyndaele JJ, van Dromme SA. Muscular weakness as side effect of botulinum toxin injection for neurogenic detrusor overactivity. Spinal Cord. 2002; 40: 599–600

    Article  PubMed  CAS  Google Scholar 

  39. Dressler D. Dysport produces intrinsically more swallowing problems than Botox: unexpected results from a conversion factor study in cervical dystonia [letter]. J Neurol Neurosurg Psychiatry. 2002; 73: 604

    Article  PubMed  CAS  Google Scholar 

  40. Carruthers A, Kleine K, Carruthers J. Botulinum A exotoxin in clinical dermatology. J Am Acad Dermatol. 1996; 34: 788–97

    Article  PubMed  CAS  Google Scholar 

  41. Carruthers J, Carruthers A. Practical cosmetic Botox techniques. J Cutan Med Surg. 1999; 3 Suppl. 4: 49–52

    Google Scholar 

  42. Alam M, Dover JS, Klein AW, et al. Botulinum a exotoxin for hyperfunctional facial lines: where not to inject. Arch Dermatol. 2002; 138: 1243–4

    Article  Google Scholar 

  43. Khawaja HA, Hemandez-Perez E. Botox in dermatology. Int J Dermatol. 2001; 40: 311–7

    Article  PubMed  CAS  Google Scholar 

  44. Rzany B, for the Expert Group. Botulinumtoxin A in der Asthetischen Dermatologie. Kosmetische Medizin. 2003; 24: 72–9

    Google Scholar 

  45. Ahn MS, Callen M, Maas CS. Temporal brow list using botulinum toxin A. Plast Reconstr Surg. 2000; 105: 112–35

    Google Scholar 

  46. Nussgens Z, Roggenkamper P. Comparison of two botulinum-toxin preparations in the treatment of essential blepharospasm. Graefes Arch Clin Exp Ophthalmol. 1997; 235: 197–9

    Article  PubMed  CAS  Google Scholar 

  47. Lew H, Yun YS, Lee SY, et al. Effect of botulinum toxin A on facial wrinkle lines in Koreans. Ophthalmologica. 2002; 216: 50–4

    Article  PubMed  CAS  Google Scholar 

  48. Hankins CL, Strimling R, Rogers GS. Botulinum A toxin for glabellar wrinkles: dose and response. Dermatol Surg. 1998; 24: 1181–3

    Article  PubMed  CAS  Google Scholar 

  49. Frankel AS. Botox for rejuvenation of the periorbital region. Facial Plast Surg. 1999; 15: 225-62

    Article  Google Scholar 

  50. Garcia A, Fulton E. Cosmetic denervation of the muscles of facial expression with botulinum toxin. Dermatol Surg. 1996; 22: 39–43

    Article  PubMed  CAS  Google Scholar 

  51. Bulstrode NW, Grobbelaar AO. Long-term prospective follow-up of botulinum toxin treatment for facial rhytides. Aesthetic Plast Surg. 2002; 26: 356–9

    Article  PubMed  CAS  Google Scholar 

  52. Kim DW, Cundiff J, Toriumi DM. Botulinum toxin A for the treatment of lateral periorbital rhytids. Facial Plast Surg North Am. 2003; 11: 445–51

    Article  Google Scholar 

  53. Vartanian AJ, Dayan SH. Complications of botulinum toxin A use in facial rejuvenation. Facial Plast Surg Clin North Am. 2003; 11: 483–92

    Article  PubMed  Google Scholar 

  54. Goldman MP. Festoon formation after infraorbital botulinum A toxin: a case report. Dermatol Surg. 2003; 29: 56–61

    Article  Google Scholar 

  55. Flynn TC, Carruthers JA, Carruthers JA, et al. Botulinum A toxin (BOTOX) in the lower eyelid: dose-finding study. Dermatol Surg. 2003; 29: 943–51

    Article  PubMed  Google Scholar 

  56. Trinidade de Almeida AR, Scuartz Cemea S. Regarding browlift with botulinum toxin [letter]. Dermatol Surg. 2001; 27: 848

    Article  Google Scholar 

  57. Klein AW. Contraindications and complications with the use of botulinum toxin. Clin Dermatol. 2004; 22: 66–75

    Article  PubMed  Google Scholar 

  58. Jeong H, Yum K-W, Lee S-S, et al. Effects of botulinum toxin type A on bilateral masseteric hypertrophy evaluated with computed tomographic measurement. Dermatol Surg. 2003; 29: 484–9

    Article  Google Scholar 

  59. Park MY, Ahn KY, Jung DS. Botulinum toxin type A treatment for contouring of the lower face. Dermatol Surg. 2003; 29: 477–83

    Article  PubMed  Google Scholar 

  60. Kim HJ, Seo K, Yum KW, et al. Effects of botulinum toxin type A on the superior cervical ganglia in rabbits. Anton Neurosci. 2002; 102: 8–12

    Article  CAS  Google Scholar 

  61. Lu L, Atchabahian A, Mackinnon SE, et al. Nerve injury with botulinum toxin. Plast Reconstr Surg. 1998; 101: 1875–80

    Article  PubMed  CAS  Google Scholar 

  62. Burguera JA, Villaroya T, Lopez-Alemany M. Polyradiculoneuritis after botulinum toxin therapy for cervical dystonia. Clin Neuropharmacol. 2000; 23: 226–8

    Article  PubMed  CAS  Google Scholar 

  63. Cobb DB, Watson WA, Fernandez MC. Botulism-like syndrome after injections of botulinum toxin. Vet Hum Toxicol. 2000; 42: 163

    PubMed  CAS  Google Scholar 

  64. Coffield JA, Considine RV, Simpson LL. The site and mechanism of action of botulinum neurotoxin. In: Janckovic J, Hallett M, editors. Therapy with botulinum toxin. New York: Marcel Dekker, 1994: 3–13

    Google Scholar 

  65. De Groot M, Schubert M, Rothe B, et al. Zentrale Effekte von Botulinumtoxin Typ A. Klin Neurophysiol. 2002; 33: 207–12

    Article  Google Scholar 

  66. Murray C, Solish N. Metallic taste: an unusual reaction to botulinum toxin A. Dermatol Surg. 2003; 29: 562–3

    Article  PubMed  Google Scholar 

  67. Dressler D, Münchau A, Bhatia KP, et al. Antibody-induced botulinum toxin therapy failure: can it be overcome by increasing botulinum toxin doses? Eur Neurol; 2002; 47: 118–21

    Article  PubMed  CAS  Google Scholar 

  68. Carruthers A, Carruthers J. Update on the botulinum neurotoxins. Skin Therapy Lett. 2001; 6: 1–2

    PubMed  CAS  Google Scholar 

  69. Wutthipan S, Kowal L, O’Day J, et al. Diplopia following subcutaneous injections of botulinum toxin A toxin for facial spasms. J Pediatr Ophthalmol Strabismus. 1997; 34: 229–34

    Google Scholar 

  70. Heckmann M, Rzany. Botulinumtoxin in der Dermatologie. Grundlagen and praktische Anwendung. München: Urban & Vogel-Medizin & Wissen, 2002

    Google Scholar 

  71. Scott AB. Preventing ptosis after botulinum treatment. Ophthal Plast Reconstr Surg. 1997; 13: 81–3

    Article  PubMed  CAS  Google Scholar 

  72. Driezen NG, Framn L. Sudden unilateral visual loss after autologous fat injection into the glabellar area. Am J Ophthalmol. 1989; 107: 85–6

    Google Scholar 

  73. Teimourian B. Blindness following fat injection. Plast Reconstr Surg. 1988; 92: 361

    Google Scholar 

  74. Sahlin S, Chen E, Kaugessar T, et al. Effect of eyelid botulinum toxin injection on lacrimal drainage. Am J Ophthalmol. 2000; 129: 481–6

    Article  PubMed  CAS  Google Scholar 

  75. Matarasso SL. Decreased tear expression with an abnormal Schirmer’s test following botulinum toxin type A for the treatment of lateral canthal rhytides. Dermatol Surg. 2002; 28: 149–52

    Article  PubMed  Google Scholar 

  76. Alam M, Dover JS, Arndt KA. Pain associated with injection of botulinum A exotoxin reconstituted using isotonic sodium chloride solution with and without preservative. Arch Dermatol. 2002; 138: 510–4

    Article  PubMed  CAS  Google Scholar 

  77. Söylev MF, Kocak N, Kuvaki B, et al. Anesthesia with EMLA® cream for botulinum A toxin injection into eyelids. Ophthalmologica. 2002; 216: 355–8

    Article  PubMed  Google Scholar 

  78. Linder JS, Edmonson BC, Laquis SJ, et al. Skin cooling before periocular botulinum toxin A injection. Ophthal Plast Reconstr Surg. 2002; 6: 441–2

    Article  Google Scholar 

  79. Harth W, Linse R. Botulinophilia: contraindication for therapy with botulinum toxin. Int J Clin Pharmacol Ther. 2001; 39: 460–3

    PubMed  CAS  Google Scholar 

  80. Brenner R, Madhusoodanan S, Kom Z, et al. Acute anxiety and depression induced by loss of sensations and muscle control after botulinum toxin A injection. South Med J. 1999; 92: 738

    Article  PubMed  CAS  Google Scholar 

  81. Roehm PC, Perry JD, Girkin CA, et al. Prevalence of periocular depigmentation after repeated botulinum toxin A injections in African American patients. J Neuroophthalmol. 1999; 19: 7–9

    Article  PubMed  CAS  Google Scholar 

  82. Karpati S, Desaknai S, Desaknai M, et al. Human herpesvirus type 8-positive facial angiosarcoma developing at the site of botulinum toxin injection for blepharospasm. Br J Dermatol. 2000; 143: 660–2

    Article  PubMed  CAS  Google Scholar 

  83. Latimer PR, Hodgkins PR, Vakalis AN, et al. Necrotising fasciitis as a complication of botulinum toxin injection. Eye. 1998; 12: 51–3

    Article  PubMed  Google Scholar 

  84. Bowden JB, Rapini RP. Psoriasiform eruption from intramuscular botulinum A toxin. Cutis. 1992; 50: 415–6

    PubMed  CAS  Google Scholar 

  85. Klein AW, Mantell A. Electromyographic guidance in injecting botulinum toxin. Dermatol Surg. 1998; 24: 1184–6

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

Author information

Authors and Affiliations

  1. Department of Dermatology, Hospital Dresden-Friedrichstadt, Academic Teaching Hospital, Friedrichstrasse 41, Dresden, 01067, Germany

    Uwe Wollina & Helga Konrad

Authors
  1. Uwe Wollina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Helga Konrad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Uwe Wollina.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wollina, U., Konrad, H. Managing Adverse Events Associated with Botulinum Toxin Type A. Am J Clin Dermatol 6, 141–150 (2005). https://doi.org/10.2165/00128071-200506030-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00128071-200506030-00001

Keywords

Search

Navigation