American Journal of Clinical Dermatology

, Volume 6, Issue 3, pp 141–150

Managing Adverse Events Associated with Botulinum Toxin Type A

A Focus on Cosmetic Procedures
Leading Article

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.

References

  1. 1.
    Tchitchikine A. Essai d’immunisation par la voie gastrointestinale contre la toxine botulique [letter]. Ann Just Pasteur. 1905; XIX: 335Google Scholar
  2. 2.
    Schantz EJ, Johnson EA. Botulinum toxin: the story of its development in human disease. Perspect Biol Med. 1997; 40: 317–27PubMedGoogle Scholar
  3. 3.
    Brin ME. Botulinum toxin: chemistry, pharmacology, toxicity, and immunology. Muscle Nerve. 1997; 20 Suppl. 6: S146–68CrossRefGoogle Scholar
  4. 4.
    Huang W, Foster JA, Rogachefsky AS. Pharmacology of botulinum toxin. J Am Acad Dermatol. 2000; 43: 249–59PubMedCrossRefGoogle Scholar
  5. 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: 1013–8PubMedCrossRefGoogle Scholar
  6. 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: 6–12PubMedCrossRefGoogle Scholar
  7. 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: 459–62PubMedGoogle Scholar
  8. 8.
    Carruthers A, Carruthers J. Cosmetic use of botulinum A exotoxin. Adv Dermatol. 1997; 12: 325-47PubMedGoogle Scholar
  9. 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: 569–72PubMedCrossRefGoogle Scholar
  10. 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: 840–9PubMedCrossRefGoogle Scholar
  11. 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: 834–40PubMedCrossRefGoogle Scholar
  12. 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: 7–13PubMedCrossRefGoogle Scholar
  13. 13.
    Niamtu J. Botulinum toxin A: a review of 1,085 oral and maxillofacial patient treatments. J Oral Maxillofac Surg. 2003; 61: 317–24PubMedCrossRefGoogle Scholar
  14. 14.
    Wilson F. Botulinum toxin-A risks overcome by proper technique. Cosmetic Surg Times 2001 Mar, 12Google Scholar
  15. 15.
    Klein AW. Complications and adverse reactions with the use of botulinum toxin. Dis Mon. 2002; 48: 336–56PubMedCrossRefGoogle Scholar
  16. 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: 43–4Google Scholar
  17. 17.
    Habbema L. Facial esthetics and patient selection. Clin Dermatol. 2004; 22: 14–7PubMedCrossRefGoogle Scholar
  18. 18.
    Carruthers A, Carruthers J. Clinical indications and injection technique for the cosmetic use of botulinum A exotoxin. Dermatol Surg. 1998; 24: 1189–94PubMedCrossRefGoogle Scholar
  19. 19.
    Matarasso SL. Complications of botulinum A exotoxin for hyperfunctional lines. Dermatol Surg. 1998; 24: 1249–54PubMedCrossRefGoogle Scholar
  20. 20.
    Li M, Goldberger BA, Hopkins C. Fatal case of BOTOX (R)-related anaphylaxis? J Forensic Sci. In pressGoogle Scholar
  21. 21.
    Cohen DE, Kaufmann JM. Hypersensitivity reactions to products and devices in plastic surgery. Facial Plast Surg Clin N Am. 2003; 11: 253–65CrossRefGoogle Scholar
  22. 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: 263–4PubMedCrossRefGoogle Scholar
  23. 23.
    Taylor SL, Hefle SL. Ingredient and labeling issues associated with allergenic foods. Allergy. 2001; 56 Suppl. 67: 64–9PubMedCrossRefGoogle Scholar
  24. 24.
    LeWitt PA, Trosch RM. Idiosyncratic reactions to intramuscular botulinum toxin type A injection. Mov Disord. 1997; 12: 1064–7PubMedCrossRefGoogle Scholar
  25. 25.
    Claus D, Druschky A, Erbguth F. Botulinum toxin: influence on respiratory heart rate variation. Mov Disord. 1995; 10: 574–9PubMedCrossRefGoogle Scholar
  26. 26.
    Malnick SD, Metchnik L, Somin M, et al. Fatal heart block following treatment with botulinum toxin for achalasia. Am J Gastroenterol. 2000; 95: 3333–4PubMedCrossRefGoogle Scholar
  27. 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: 249–54PubMedCrossRefGoogle Scholar
  28. 28.
    Wollina U. Botulinum A toxin for wrinkles: release from tension headache. J Fur Acad Dermatol Venereol. 2000; 14: 142–3CrossRefGoogle Scholar
  29. 29.
    Silberstein S, Mathew N, Saper J, et al. Botulinum toxin type A as a safe migraine preventive treatment. Headache. 2000; 40: 445–50PubMedCrossRefGoogle Scholar
  30. 30.
    Patel MP, Talmor M, Nolan WB. Botox and collagen for glabellar furrows: advantages of combination therapy. Ann Plast Surg. 2004; 52: 442–7PubMedCrossRefGoogle Scholar
  31. 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: 62–5PubMedCrossRefGoogle Scholar
  32. 32.
    Goldman A. Botulinum toxin in plastic surgery: experience and indications in 1200 treated areas. Rev Soc Bras Cir Past Sao Paulo. 1999; 14: 21–30Google Scholar
  33. 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: 233–9Google Scholar
  34. 34.
    Fiacchino F, Grandi L, Soliveri P, et al. Sensitivity to vecuronium after botulinum toxin administration. J Neurosurg Anesthesiol. 1997; 9: 149–53PubMedCrossRefGoogle Scholar
  35. 35.
    Matarasso A, Deva AK, and the American Society of Plastic Surgeons DATA Committee. Botulinum toxin. Plast Reconstr Surg. 2002; 109: 1191–7PubMedCrossRefGoogle Scholar
  36. 36.
    Letessier S. Treatment of wrinkles with botulinum toxin. J Dermatol Treat. 1999; 10: 31–6CrossRefGoogle Scholar
  37. 37.
    Sunness JS, Kelman S. Cosmetic Botox injection mimicking myasthenia gravis. Plast Reconstr Surg. 2004; 113: 1515PubMedGoogle Scholar
  38. 38.
    Wyndaele JJ, van Dromme SA. Muscular weakness as side effect of botulinum toxin injection for neurogenic detrusor overactivity. Spinal Cord. 2002; 40: 599–600PubMedCrossRefGoogle Scholar
  39. 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: 604PubMedCrossRefGoogle Scholar
  40. 40.
    Carruthers A, Kleine K, Carruthers J. Botulinum A exotoxin in clinical dermatology. J Am Acad Dermatol. 1996; 34: 788–97PubMedCrossRefGoogle Scholar
  41. 41.
    Carruthers J, Carruthers A. Practical cosmetic Botox techniques. J Cutan Med Surg. 1999; 3 Suppl. 4: 49–52Google Scholar
  42. 42.
    Alam M, Dover JS, Klein AW, et al. Botulinum a exotoxin for hyperfunctional facial lines: where not to inject. Arch Dermatol. 2002; 138: 1243–4CrossRefGoogle Scholar
  43. 43.
    Khawaja HA, Hemandez-Perez E. Botox in dermatology. Int J Dermatol. 2001; 40: 311–7PubMedCrossRefGoogle Scholar
  44. 44.
    Rzany B, for the Expert Group. Botulinumtoxin A in der Asthetischen Dermatologie. Kosmetische Medizin. 2003; 24: 72–9Google Scholar
  45. 45.
    Ahn MS, Callen M, Maas CS. Temporal brow list using botulinum toxin A. Plast Reconstr Surg. 2000; 105: 112–35Google Scholar
  46. 46.
    Nussgens Z, Roggenkamper P. Comparison of two botulinum-toxin preparations in the treatment of essential blepharospasm. Graefes Arch Clin Exp Ophthalmol. 1997; 235: 197–9PubMedCrossRefGoogle Scholar
  47. 47.
    Lew H, Yun YS, Lee SY, et al. Effect of botulinum toxin A on facial wrinkle lines in Koreans. Ophthalmologica. 2002; 216: 50–4PubMedCrossRefGoogle Scholar
  48. 48.
    Hankins CL, Strimling R, Rogers GS. Botulinum A toxin for glabellar wrinkles: dose and response. Dermatol Surg. 1998; 24: 1181–3PubMedCrossRefGoogle Scholar
  49. 49.
    Frankel AS. Botox for rejuvenation of the periorbital region. Facial Plast Surg. 1999; 15: 225-62CrossRefGoogle Scholar
  50. 50.
    Garcia A, Fulton E. Cosmetic denervation of the muscles of facial expression with botulinum toxin. Dermatol Surg. 1996; 22: 39–43PubMedCrossRefGoogle Scholar
  51. 51.
    Bulstrode NW, Grobbelaar AO. Long-term prospective follow-up of botulinum toxin treatment for facial rhytides. Aesthetic Plast Surg. 2002; 26: 356–9PubMedCrossRefGoogle Scholar
  52. 52.
    Kim DW, Cundiff J, Toriumi DM. Botulinum toxin A for the treatment of lateral periorbital rhytids. Facial Plast Surg North Am. 2003; 11: 445–51CrossRefGoogle Scholar
  53. 53.
    Vartanian AJ, Dayan SH. Complications of botulinum toxin A use in facial rejuvenation. Facial Plast Surg Clin North Am. 2003; 11: 483–92PubMedCrossRefGoogle Scholar
  54. 54.
    Goldman MP. Festoon formation after infraorbital botulinum A toxin: a case report. Dermatol Surg. 2003; 29: 56–61CrossRefGoogle Scholar
  55. 55.
    Flynn TC, Carruthers JA, Carruthers JA, et al. Botulinum A toxin (BOTOX) in the lower eyelid: dose-finding study. Dermatol Surg. 2003; 29: 943–51PubMedCrossRefGoogle Scholar
  56. 56.
    Trinidade de Almeida AR, Scuartz Cemea S. Regarding browlift with botulinum toxin [letter]. Dermatol Surg. 2001; 27: 848CrossRefGoogle Scholar
  57. 57.
    Klein AW. Contraindications and complications with the use of botulinum toxin. Clin Dermatol. 2004; 22: 66–75PubMedCrossRefGoogle Scholar
  58. 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: 484–9CrossRefGoogle Scholar
  59. 59.
    Park MY, Ahn KY, Jung DS. Botulinum toxin type A treatment for contouring of the lower face. Dermatol Surg. 2003; 29: 477–83PubMedCrossRefGoogle Scholar
  60. 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: 8–12CrossRefGoogle Scholar
  61. 61.
    Lu L, Atchabahian A, Mackinnon SE, et al. Nerve injury with botulinum toxin. Plast Reconstr Surg. 1998; 101: 1875–80PubMedCrossRefGoogle Scholar
  62. 62.
    Burguera JA, Villaroya T, Lopez-Alemany M. Polyradiculoneuritis after botulinum toxin therapy for cervical dystonia. Clin Neuropharmacol. 2000; 23: 226–8PubMedCrossRefGoogle Scholar
  63. 63.
    Cobb DB, Watson WA, Fernandez MC. Botulism-like syndrome after injections of botulinum toxin. Vet Hum Toxicol. 2000; 42: 163PubMedGoogle Scholar
  64. 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: 3–13Google Scholar
  65. 65.
    De Groot M, Schubert M, Rothe B, et al. Zentrale Effekte von Botulinumtoxin Typ A. Klin Neurophysiol. 2002; 33: 207–12CrossRefGoogle Scholar
  66. 66.
    Murray C, Solish N. Metallic taste: an unusual reaction to botulinum toxin A. Dermatol Surg. 2003; 29: 562–3PubMedCrossRefGoogle Scholar
  67. 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: 118–21PubMedCrossRefGoogle Scholar
  68. 68.
    Carruthers A, Carruthers J. Update on the botulinum neurotoxins. Skin Therapy Lett. 2001; 6: 1–2PubMedGoogle Scholar
  69. 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: 229–34Google Scholar
  70. 70.
    Heckmann M, Rzany. Botulinumtoxin in der Dermatologie. Grundlagen and praktische Anwendung. München: Urban & Vogel-Medizin & Wissen, 2002Google Scholar
  71. 71.
    Scott AB. Preventing ptosis after botulinum treatment. Ophthal Plast Reconstr Surg. 1997; 13: 81–3PubMedCrossRefGoogle Scholar
  72. 72.
    Driezen NG, Framn L. Sudden unilateral visual loss after autologous fat injection into the glabellar area. Am J Ophthalmol. 1989; 107: 85–6Google Scholar
  73. 73.
    Teimourian B. Blindness following fat injection. Plast Reconstr Surg. 1988; 92: 361Google Scholar
  74. 74.
    Sahlin S, Chen E, Kaugessar T, et al. Effect of eyelid botulinum toxin injection on lacrimal drainage. Am J Ophthalmol. 2000; 129: 481–6PubMedCrossRefGoogle Scholar
  75. 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: 149–52PubMedCrossRefGoogle Scholar
  76. 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: 510–4PubMedCrossRefGoogle Scholar
  77. 77.
    Söylev MF, Kocak N, Kuvaki B, et al. Anesthesia with EMLA® cream for botulinum A toxin injection into eyelids. Ophthalmologica. 2002; 216: 355–8PubMedCrossRefGoogle Scholar
  78. 78.
    Linder JS, Edmonson BC, Laquis SJ, et al. Skin cooling before periocular botulinum toxin A injection. Ophthal Plast Reconstr Surg. 2002; 6: 441–2CrossRefGoogle Scholar
  79. 79.
    Harth W, Linse R. Botulinophilia: contraindication for therapy with botulinum toxin. Int J Clin Pharmacol Ther. 2001; 39: 460–3PubMedGoogle Scholar
  80. 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: 738PubMedCrossRefGoogle Scholar
  81. 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: 7–9PubMedCrossRefGoogle Scholar
  82. 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: 660–2PubMedCrossRefGoogle Scholar
  83. 83.
    Latimer PR, Hodgkins PR, Vakalis AN, et al. Necrotising fasciitis as a complication of botulinum toxin injection. Eye. 1998; 12: 51–3PubMedCrossRefGoogle Scholar
  84. 84.
    Bowden JB, Rapini RP. Psoriasiform eruption from intramuscular botulinum A toxin. Cutis. 1992; 50: 415–6PubMedGoogle Scholar
  85. 85.
    Klein AW, Mantell A. Electromyographic guidance in injecting botulinum toxin. Dermatol Surg. 1998; 24: 1184–6PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Department of DermatologyHospital Dresden-Friedrichstadt, Academic Teaching HospitalDresdenGermany

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