Title True Allergic Reaction to Amide Local Anesthetics Such as Lidocaine Is Confirmed by Immunologic Testing
Clinical Question For patients receiving injection of an amide local anesthetic such as lidocaine, is there a risk of true allergic reaction versus a pseudoallergic psychogenic response, and can this be confirmed as an immunologic reaction to the anesthetic agent itself and not to known additives or preservatives?
Clinical Bottom Line True allergy to amide local anesthetics such as lidocaine does exist and has been documented as type I and IV hypersensitivity reactions; however, the occurrence of this allergy in the population has been shown to be less than 1%. This should be differentiated from more common psychogenic responses to injection such as vasovagal syncope or anxiety. Differentiation from allergy due purely to the local anesthetic or to contained preservatives or both could not be distinguished in these studies. In the case of true allergic reaction to any dental injection, referral for a more comprehensive allergy test should be considered.
Best Evidence  
PubMed ID Author / Year Patient Group Study type
(level of evidence)
19402039Fuzier/2009293 reports of allergy to local anesthetic/11 confirmedRetrospective records review
Key resultsReports from two French databases, the Pharmacovigilance database and the GERAP database, identified 16 cases of true allergic reaction as confirmed by patch test and/or skin prick test and/or challenge test to amide local anesthetics. 11 of these cases were immediate type I allergic reactions and occurred within 1 hour. The remaining 5 cases were delayed type IV reactions and occurred within 6 hours to 1 month after local anesthetic administration. A majority of these cases (11/16) were due to lidocaine and included both type I and type IV reactions. Any differences in the lidocaine formulation used in France compared to lidocaine used in the US were not mentioned. No patient risk factors were reported and although common preservatives such as bisulphites, parabens, carboxymethylcellulose, and para-aminobenzoic acid were mentioned, they were not tested separately and thus cannot be ruled out as noncontributory.
21623805Sambrook/2011221 reported adverse reactions/16 cases of true allergic reactionRetrospective records review
Key results221 adverse reactions to local anesthetics reported to the Office of Product Review of the Therapeutic Goods Administration (TGA) of Australia. Of these 221 cases, 16 cases or 7% were reported type I IgE-mediated immunologic reactions. Other reported adverse reactions easily perceived as “allergy” to patients were: syncope in 59 cases or 27%; CNS responses such as depression, agitation, and tremor reported in 36 cases or 16%; and cardiovascular responses including angina and myocardial infarction in 19 cases or 9%. Data for follow-up allergy testing of true type I allergic reactions, as well as patient risk factors, were not included. Reporting occurred over 35 years for which the author assumes 10 million cartridges of local anesthetic were administered per year. Thus, the 16 cases of true allergy represents 1 in 22 million local anesthetic injections or an occurrence of significantly less than 1%. Any differences in Australian local anesthetic formulations compared with those used in the US were not mentioned.
18234312Venemalm/20081 patientCase report
Key resultsA 31-year old woman was given 2 cartridges of 3% mepivicaine prior to dental treatment as well as lidocaine gel. Within minutes, pruritus with nausea, vomiting, GI disturbances, and a brief loss of consciousness occurred as well as erythema and swelling of the hands. Intradermal and in vitro testing confirmed an IgE-mediated type I anaphylactic reaction to mepivicaine, an amide local anesthetic. No patient risk factors were reported, and an alternative local anesthetic was not considered or tested. Despite mention of the preservatives metabisulfite and methylparaben, specific and separate testing was not discussed and thus cannot be ruled as noncontributory.
19402039Noormalin/20051 patientCase report
Key resultsUpon receiving lidocaine dental gel and 2% lidocaine HCL with epinephrine injection for a dental procedure, a 7 year-old female experienced facial swelling. IV antihistamine was given and the swelling subsided. True IgE-mediated Type I hypersensitivity to lidocaine HCL was confirmed by skin prick test (SPT). No patient risk factors were reported, and an alternative local anesthetic was not considered or tested.
Evidence Search ("Anesthesia, Dental/adverse effects"[Mesh] AND "Hypersensitivity"[Mesh]) AND "Anesthetics, Local"[Mesh] OR ("Anesthetics, Local"[Mesh] AND "hypersensitivity, delayed"[Mesh] AND "hypersensitivity, immediate"[Mesh]) OR "hypersensitivity/immunology"[Mesh] AND "anesthetics, local"[Mesh]
Comments on
The Evidence
Validity: The studies by Fuzier and Sambrook were retrospective in nature and did not include randomization; however, both compiled data from large national databases over extended periods of many years. The follow-up of reported allergic reactions with allergy testing to confirm true allergy also strengthens data reported in the Fuzier study; however, this follow-up was not included in the Sambrook study. The claim that true allergy to amide local anesthetics commonly used in dentistry is indeed present in the general population (although rare) is supported by evidence. The two included case reports describe occurrence of known symptoms characteristic of true allergic reaction and were cited by a majority of the literature on this topic. The apparent female predilection based on the subjects of both case reports, although also observed and noted in the Fuzier study, has not yet been investigated on its own and thus at this point can only be considered a coincidence. Perspective: Although both articles that analyzed reports of adverse reactions present a seemingly high number of allergic reactions, these numbers must be considered relative to much higher numbers of nonallergic adverse reactions to local anesthetics injection as well as to suspected allergic reactions that could not be confirmed by follow-up allergy testing. Overall, the evidence presented here suggests a very low occurrence of true allergy to local anesthetic injection, which aligns with what is observed clinically.
Applicability The data presented shows the occurrence of true allergy to local anesthetics used for dental injections to be less than 1%. Despite the rarity of its occurrence, however, true allergy of both type I and IV immune hypersensitivity reactions does in fact exist. While the extremely low occurrence of these reactions may be dismissed as common knowledge based on clinical experience, it is necessary to definitively establish and legitimize this characteristic of commonly used amide local anesthetics such as lidocaine. Despite the low occurrence of true allergy to local anesthetic injection, it is common for patients to report an “allergy” to dental injections. It’s important to realize that in many cases this may be a pseudoallergy - in reality, a psychogenic response to receiving any injection regardless of its contents. However, clinicians must also keep in mind that for some patients, true allergy may in fact occur and thus a detailed assessment of past allergic reactions and any history of allergy testing must be made. If the dentist cannot make a definitive assessment, referral for allergy testing such as a skin prick test as used in the presented evidence should be considered before moving forward with treatment.
Specialty (Oral Medicine/Pathology/Radiology) (Endodontics) (General Dentistry) (Oral Surgery) (Orthodontics) (Pediatric Dentistry) (Periodontics) (Prosthodontics) (Restorative Dentistry)
Keywords Local anesthetic, amide local anesthetic, lidocaine, mepivicaine, allergy, hypersensitivity, adverse effects
ID# 3062
Date of submission 04/08/2016
E-mail hermannrh@livemail.uthscsa.edu
Author Robert H. Hermann
Co-author(s) e-mail
Faculty mentor Gregory Spackman, DDS, MBA & Dr. Francis Lam
Faculty mentor e-mail SPACKMAN@uthscsa.edu; LAMF@uthscsa.edu
Basic Science Rationale
(Mechanisms that may account for and/or explain the clinical question, i.e. is the answer to the clinical question consistent with basic biological, physical and/or behavioral science principles, laws and research?)
None available
Comments and Evidence-Based Updates on the CAT
None available