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Allergic reactions to local anesthetics

Michael Schatz, MD, MS
Section Editor
N Franklin Adkinson, Jr, MD
Deputy Editor
Anna M Feldweg, MD


Local anesthetics (LAs) have been used to provide anesthesia since the discovery of cocaine in 1884 [1]. They may be administered by topical, infiltrative, nerve block, epidural, or spinal routes [1]. Adverse reactions to LAs are not uncommon and most are nonallergic in etiology. However, allergic reactions to LAs can occur, and the evaluation and management of patients with these reactions will be reviewed here. A related topic, anaphylaxis in the setting of anesthesia or surgery, is found separately. (See "Perioperative anaphylaxis: Clinical manifestations, etiology, and management" and "Perioperative anaphylaxis: Evaluation and prevention of recurrent reactions".)

The use of LAs for infiltrative anesthesia and for topical anesthesia and a general approach to the management of pain and sedation in children are discussed elsewhere. (See "Subcutaneous infiltration of local anesthetics" and "Topical anesthetics in children" and "Procedural sedation in children outside of the operating room".)


Two distinct types of allergic reactions to local anesthetics (LAs) have been described:

Allergic contact dermatitis and delayed swelling at the site of administration – These types of reactions are well established. (See "Common allergens in allergic contact dermatitis", section on 'Anesthetics'.)

Urticaria and anaphylaxis – These types of reaction are rare and the data implicating LAs are limited to case reports.

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Literature review current through: Sep 2017. | This topic last updated: Feb 12, 2016.
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  1. Eggleston ST, Lush LW. Understanding allergic reactions to local anesthetics. Ann Pharmacother 1996; 30:851.
  2. Melamed J, Beaucher WN. Delayed-type hypersensitivity (type IV) reactions in dental anesthesia. Allergy Asthma Proc 2007; 28:477.
  3. Weightman W, Turner T. Allergic contact dermatitis from lignocaine: report of 29 cases and review of the literature. Contact Dermatitis 1998; 39:265.
  4. García F, Iparraguirre A, Blanco J, et al. Contact dermatitis from prilocaine with cross-sensitivity to pramocaine and bupivacaine. Contact Dermatitis 2007; 56:120.
  5. Pérez-Pérez LC, Fernández-Redondo V, Ginarte-Val M, et al. Allergic contact dermatitis from EMLA cream in a hemodialyzed patient. Dermatitis 2006; 17:85.
  6. Mackley CL, Marks JG Jr, Anderson BE. Delayed-type hypersensitivity to lidocaine. Arch Dermatol 2003; 139:343.
  7. Amado A, Sood A, Taylor JS. Contact allergy to lidocaine: a report of sixteen cases. Dermatitis 2007; 18:215.
  8. Sood A, Taylor JS. Bacitracin: allergen of the year. Am J Contact Dermat 2003; 14:3.
  9. Grandinetti PJ, Fowler JF Jr. Simultaneous contact allergy to neomycin, bacitracin, and polymyxin. J Am Acad Dermatol 1990; 23:646.
  10. Connolly M, Mehta A, Sansom JE, Dunnill MG. Allergic contact dermatitis from tetracaine in the beauty industry. Contact Dermatitis 2004; 51:95.
  11. Villarreal LC, de Frutos FJ, Del Prado Sánchez Caminero M, Sebastián FV. Perineal allergic contact dermatitis due to tetracaine in a urological lubricant. Contact Dermatitis 2004; 51:321.
  12. Gehrig KA, Warshaw EM. Allergic contact dermatitis to topical antibiotics: Epidemiology, responsible allergens, and management. J Am Acad Dermatol 2008; 58:1.
  13. Gallenkemper G, Rabe E, Bauer R. Contact sensitization in chronic venous insufficiency: modern wound dressings. Contact Dermatitis 1998; 38:274.
  14. Schwartz HJ, Sher TH. Bisulfite sensitivity manifesting as allergy to local dental anesthesia. J Allergy Clin Immunol 1985; 75:525.
  15. Dooms-Goossens A, de Alam AG, Degreef H, Kochuyt A. Local anesthetic intolerance due to metabisulfite. Contact Dermatitis 1989; 20:124.
  16. Fisher AA. Reactions to injectable local anesthetics. Part IV: Reactions to sulfites in local anesthetics. Cutis 1989; 44:283.
  17. Goldfarb G, Simon R. Provocation of sulfite sensitive asthma (Abst). J Allergy Clin Immunol 1984; 73:135.
  18. Ivy RS. Anesthetics and methylparaben. J Am Dent Assoc 1983; 106:302.
  19. Cashman AL, Warshaw EM. Parabens: a review of epidemiology, structure, allergenicity, and hormonal properties. Dermatitis 2005; 16:57.
  20. Pratt MD, Belsito DV, DeLeo VA, et al. North American Contact Dermatitis Group patch-test results, 2001-2002 study period. Dermatitis 2004; 15:176.
  21. Condie MW, Adams RM. Influence of oral prednisone on patch-test reactions to Rhus antigen. Arch Dermatol 1973; 107:540.
  22. Kaufmann JM, Hale EK, Ashinoff RA, Cohen DE. Cutaneous lidocaine allergy confirmed by patch testing. J Drugs Dermatol 2002; 1:192.
  23. Sanchez-Morillas L, Martinez JJ, Martos MR, et al. Delayed-type hypersensitivity to mepivacaine with cross-reaction to lidocaine. Contact Dermatitis 2005; 53:352.
  24. www.truetest.com/PhysicianPDF/HCP8_TT_Rx_info.pdf (Accessed on November 21, 2008).
  25. Bircher AJ, Messmer SL, Surber C, Rufli T. Delayed-type hypersensitivity to subcutaneous lidocaine with tolerance to articaine: confirmation by in vivo and in vitro tests. Contact Dermatitis 1996; 34:387.
  26. Curley RK, Macfarlane AW, King CM. Contact sensitivity to the amide anesthetics lidocaine, prilocaine, and mepivacaine. Case report and review of the literature. Arch Dermatol 1986; 122:924.
  27. Klein CE, Gall H. Type IV allergy to amide-type local anesthetics. Contact Dermatitis 1991; 25:45.
  28. Ing Lorenzini K, Gay-Crosier Chabry F, Piguet C, Desmeules J. Meta-xylene: identification of a new antigenic entity in hypersensitivity reactions to local anesthetics. J Allergy Clin Immunol Pract 2016; 4:162.
  29. www.truetest.com (Accessed on November 21, 2008).
  30. Cuesta-Herranz J, de las Heras M, Fernández M, et al. Allergic reaction caused by local anesthetic agents belonging to the amide group. J Allergy Clin Immunol 1997; 99:427.
  31. Waton J, Boulanger A, Trechot PH, et al. Contact urticaria from Emla cream. Contact Dermatitis 2004; 51:284.
  32. Haugen RN, Brown CW. Case reports: type I hypersensitivity to lidocaine. J Drugs Dermatol 2007; 6:1222.
  33. Chiu CY, Lin TY, Hsia SH, et al. Systemic anaphylaxis following local lidocaine administration during a dental procedure. Pediatr Emerg Care 2004; 20:178.
  34. Warrington RJ, McPhillips S. Allergic reaction to local anesthetic agents of the amide group. J Allergy Clin Immunol 1997; 100:855.
  35. Morais-Almeida M, Gaspar A, Marinho S, Rosado-Pinto J. Allergy to local anesthetics of the amide group with tolerance to procaine. Allergy 2003; 58:827.
  36. Calderon AL, Diot N, Benatir F, et al. Immediate allergic cross-reactivity to levobupivacaine and ropivacaine. Anaesthesia 2013; 68:203.
  37. Dower JS Jr. A review of paresthesia in association with administration of local anesthesia. Dent Today 2003; 22:64.
  38. Fiset L, Milgrom P, Weinstein P, et al. Psychophysiological responses to dental injections. J Am Dent Assoc 1985; 111:578.
  39. Cawson RA, Curson I, Whittington DR. The hazards of dental local anaesthetics. Br Dent J 1983; 154:253.
  40. Chernow B, Balestrieri F, Ferguson CD, et al. Local dental anesthesia with epinephrine. Minimal effects on the sympathetic nervous system or on hemodynamic variables. Arch Intern Med 1983; 143:2141.
  41. Latronica RJ, Goldberg AF, Wightman JR. Local anesthetic sensitivity. Report of a case. Oral Surg Oral Med Oral Pathol 1969; 28:439.
  42. Wells JP, Beckett H. Articaine hydrochloride: a safe alternative to lignocaine? Dent Update 2008; 35:253.
  43. Lin FL, Woodmansee D, Patterson R. Near-fatal anaphylaxis to topical bacitracin ointment. J Allergy Clin Immunol 1998; 101:136.
  44. Schroer BC, Fox CC, Hauswirth DW. Skin testing after anaphylaxis to a topical Neosporin preparation. Ann Allergy Asthma Immunol 2008; 101:444.
  45. Sharif S, Goldberg B. Detection of IgE antibodies to bacitracin using a commercially available streptavidin-linked solid phase in a patient with anaphylaxis to triple antibiotic ointment. Ann Allergy Asthma Immunol 2007; 98:563.
  46. Nasser SM, Ewan PW. Opiate-sensitivity: clinical characteristics and the role of skin prick testing. Clin Exp Allergy 2001; 31:1014.
  47. Nagel JE, Fuscaldo JT, Fireman P. Paraben allergy. JAMA 1977; 237:1594.
  48. Aldrete JA, Johnson DA. Allergy to local anesthetics. JAMA 1969; 207:356.
  49. Johnson WT, DeStigter T. Hypersensitivity to procaine, tetracaine, mepivacaine, and methylparaben: report of a case. J Am Dent Assoc 1983; 106:53.
  50. Luebke NH, Walker JA. Discussion of sensitivity to preservatives in anesthetics. J Am Dent Assoc 1978; 97:656.
  51. Macy E, Schatz M, Zeiger RS. Immediate hypersensitivity to methylparaben causing false-positive results of local anesthetic skin testing or provocative dose testing. The Permanente Journal 2002; 6:17.
  52. Russo PA, Banovic T, Wiese MD, et al. Systemic allergy to EDTA in local anesthetic and radiocontrast media. J Allergy Clin Immunol Pract 2014; 2:225.
  53. Schatz M. Adverse reactions to local anesthetics. Immunol All Clin N Am 1992; 12:585.
  54. Barer MR, McAllen MK. Hypersensitivity to local anaesthetics: a direct challenge test with lignocaine for definitive diagnosis. Br Med J (Clin Res Ed) 1982; 284:1229.
  55. Ravindranathan N. Allergic reaction to lignocaine. A case report. Br Dent J 1975; 138:101.
  56. Mertes PM, Malinovsky JM, Jouffroy L, et al. Reducing the risk of anaphylaxis during anesthesia: 2011 updated guidelines for clinical practice. J Investig Allergol Clin Immunol 2011; 21:442.
  57. Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology, Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol 2010; 105:259.
  58. deShazo RD, Nelson HS. An approach to the patient with a history of local anesthetic hypersensitivity: experience with 90 patients. J Allergy Clin Immunol 1979; 63:387.
  59. Chandler MJ, Grammer LC, Patterson R. Provocative challenge with local anesthetics in patients with a prior history of reaction. J Allergy Clin Immunol 1987; 79:883.
  60. Sindel LJ, deShazo RD. Accidents resulting from local anesthetics. True or false allergy? Clin Rev Allergy 1991; 9:379.
  61. Gall H, Kaufmann R, Kalveram CM. Adverse reactions to local anesthetics: analysis of 197 cases. J Allergy Clin Immunol 1996; 97:933.
  62. Fisher MM, Bowey CJ. Alleged allergy to local anaesthetics. Anaesth Intensive Care 1997; 25:611.
  63. Lorenzi P, Marsili M, Manetta G, et al. Prevention of anaphylactic-anaphylactoid reactions to anesthetics in high-risk allergic patients. Anesth Pain Control Dent 1993; 2:227.
  64. Troise C, Voltolini S, Minale P, et al. Management of patients at risk for adverse reactions to local anesthetics: analysis of 386 cases. J Investig Allergol Clin Immunol 1998; 8:172.
  65. Wasserfallen JB, Frei PC. Long-term evaluation of usefulness of skin and incremental challenge tests in patients with history of adverse reaction to local anesthetics. Allergy 1995; 50:162.