Q:

5/29/2014
A bit of an unusual question: Given both Cocaine and novocain are benzoid acid derivatives, can I assume a patient with a remote (30 years ago) history of anaphyalxis (immediate facial swelling, shortness of breath, hives, requiring EMS transport to hospital) to novocain who has since smoked crack for many years (sober for 16) would likely tolerate novocain now? I'm reluctant to test given history, but she had a severe reaction to lidocaine last week and needs dental work urgently. She is very certain novocain was the original offending drug, and records indicate lidocaine was clearly used last week.

A:

Thank you for your inquiry.

In brief, and in direct answer to your question, no, you cannot assume carte blanche that your patient can tolerate novocaine because she can tolerate cocaine. Unfortunately, not enough is known about the potential allergenic crossreactivity between these two agents. Thus, I believe your only option would be to perform a skin test/provocative challenge procedure.

Since, at least based upon the literature, amides are less likely to produce true IgE-mediated events than paraaminobenzoic acid derivatives, I would perform this procedure using an amide anesthetic. I would also be suspicious that perhaps the reaction that was purportedly due to lidocaine was not a true anaphylactic response because such reactions are very rare. However, they have been reported. Here is a link to one such report.

In this article you will find a skin test and challenge procedure employing amide anesthetics. Using this technique the authors were able to safely identify a local anesthetic their patient could tolerate. Also, the more traditional application of a skin test/provocative challenge technique using a single anesthetic is described in several of the articles copied below. In these articles, an amide anesthetic to which the patient has not reacted adversely is selected at random, and it is the only one employed for the procedure. In the article accessed by the link above, several local anesthetics were skin tested simultaneously, and the agent demonstrating a negative skin test was employed. This of course is based upon the assumption that a true IgE-mediated reaction to lidocaine was responsible for the reaction in this patient and, as mentioned, such must be extremely rare. Thus, in most instances, we simply employ a single agent, do skin testing as described in the references below, and then perform a graded challenge procedure. This procedure has been extremely safe.

In summary, I would test to either one or more amide anesthetics as described in the references discussed above, and then proceed with a graded challenge. In our experience, these procedures have been done without adverse event, and allow the patient to receive a local anesthetic.

Thank you again for your inquiry and we hope this response is helpful to you.

Hwangbo et al. Successful Finding of Local Anesthetics for a Girl with Local Lidocaine Anaphylaxis. Pediat Therapeut 2013, 3:1.

Anesth Prog. 2006 Fall; 53(3): 98–109.
doi: 10.2344/0003-3006(2006)53[98:EOLAP]2.0.CO;2
PMCID: PMC1693664
Daniel E Becker
Essentials of Local Anesthetic Pharmacology

Schatz M. Adverse reactions to local anesthetics. Immunol Allergy Clin North Am. 1992;12:585–609
J Allergy Clin Immunol. 1984 Oct;74(4 Pt 2):606-16.
Skin testing and incremental challenge in the evaluation of adverse reactions to local anesthetics.
Schatz M.
Abstract
True allergic reactions to local anesthetics (LAs) probably make up no more than 1% of all adverse LA reactions. A diagnosis of true potential allergic reactivity is made difficult because (1) the history of the prior reaction may be vague or equivocal and (2) the lack of identification of the actual specific LA hapten-carrier complex limits the potential usefulness of immunologic tests. Nonetheless, since avoidance of LAs may be associated with substantial increased pain or increased risk and because true allergic reactions are rare, investigators and clinicians have used skin testing, incremental challenge, or both as a means of identifying a safe LA for a patient with a history of a prior adverse reaction. Review of the literature dealing with LA skin testing and incremental challenge suggests the following: (1) Skin testing with LAs may correlate with a history of an adverse reaction but may produce systemic adverse reactions, especially with undiluted drug. (2) Although false positive skin tests have been reported, most skin-tested patients who subsequently tolerate an LA have a negative skin test to that drug, and false negative skin tests have not been clearly documented. (3) Incremental challenge beginning with diluted LA is a safe and effective means of identifying a drug that a patient with a history of a prior adverse reaction can tolerate. (4) Current concepts of non-cross-reacting LA groups may be useful in the choice of a drug for use in skin testing and incremental challenge. (5) Preservatives in LAs may account for some but probably not the majority of adverse reactions to LAs. On the basis of this literature review, a practical protocol including dilutional skin testing and incremental challenge is presented for use in evaluating patients with prior adverse reactions to LAs.

Ann Allergy Asthma Immunol. 2003 Oct;91(4):342-5.
Evaluation of adverse reactions to local anesthetics: experience with 236 patients.
Berkun Y, Ben-Zvi A, Levy Y, Galili D, Shalit M.
Source
Department of Pediatrics, Bikur Cholim Hospital, Jerusalem, Israel.
Abstract
Background: Adverse reactions to local anesthetics (LAs) are frequently reported. Although most of these reactions are not immune mediated, many patients are referred to allergy clinics and undergo extensive evaluation.
Objective: To determine the prevalence of true LA allergy among the patients referred for suspected hypersensitivity and to evaluate the usefulness of the currently used evaluation protocol.
Methods: A total of 236 patients referred to our allergy clinic for investigation of LA hypersensitivity were included in this study. The evaluation protocol was composed of skin prick and intradermal tests, followed by subcutaneous challenge with unrelated LA preparations that contained preservatives.
Results: Skin prick and intradermal test results were negative for all subjects. No objective adverse reactions were observed during the challenge in all but 1 patient, who developed local erythema at the site of injection and later underwent an uneventful challenge with a different LA.
Conclusions: Allergic reactions were not reproduced during testing and challenge with LA preparations that contained preservatives or preservatives with adrenaline in our large group of patients with suspected LA allergy. Since both prick and intradermal skin test results were negative in all the patients and did not provide us with useful information, we propose to modify the standard protocol by omitting intradermal tests and shortening the challenge. We also suggest that the whole procedure be performed with LAs that contain preservatives, which are usually the preferred preparations widely used in daily practice.

Am J Med Sci. 2007 Sep; 334(3):190-6.
Approach to patients with suspected hypersensitivity to local anesthetics.
Phillips JF, Yates AB, Deshazo RD.
Source
Department of Pediatrics, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Abstract
Adverse reactions to local anesthetics are relatively common, but true IgE-mediated hypersensitivity is extremely rare. Fortunately, the vast majority of adverse reactions occur via nonimmunologic means, but considerable confusion still exists among providers. We conducted a review of the literature to determine if earlier estimates of IgE-mediated allergy are consistent with current reports and whether current management strategies are consistent with these findings. We identified several confounding variables involved in the evaluation, including the roles of preservatives/additives, epinephrine, latex, and inadequate testing procedures. These problems may cause significant diagnostic challenges for clinicians. It is in fact much more likely that there is an alternate diagnosis, and in many cases clinicians can begin the evaluation in the office. When local anesthetic allergy is still suspected, the patient should be referred to an allergist for testing to determine if the suspected culprit drug can be safely used, or, if necessary, identify a suitable alternative.

Gal et al: Adverse reactions to local anesthetics: Analysis of 197 cases. Journal of Allergy and Clinical Immunology Vol. 97, Issue 4, Pages 933-937
Background: Adverse drug reactions to local anesthetics are frequently reported. However, little is known about the underlying mechanisms. Therefore we investigated 177 patients with a history of 197 events after application of these drugs.
Methods: The diagnostic approach included prick and intracutaneous tests, provocative challenge tests with causative and unrelated local anesthetics, and in selected cases, radioimmunoassays to detect specific IgE. In addition, tests were performed with preservatives, including sodium metabisulfite and parahydroxybenzoic acid ester.
Results: Results of prick and intracutaneous tests with local anesthetics were all negative. Only three patients reacted after subcutaneous challenge with the causative drug (local anesthetics of the amide type). Although one patient showed a delayed-type response to mepivacaine, two patients had immediate-type reactions to articaine and lidocaine. However, in both cases no specific IgE could be detected. In five patients with positive skin test reactions to preservatives, challenge test results remained negative.
Conclusions: Two immediate-type reactions were not IgE-mediated. In only one of 197 reported adverse reactions were we able to prove delayed-type allergic response. Therefore true allergic reactions caused by local anesthetics are extremely rare.

Stahl MC et al: IgE-Mediated Reactions to Local Anesthetics: a Case Report.The Journal of Allergy and Clinical Immunology
Volume 127, Issue 2, Supplement , Page AB193, February 2011
Rationale: IgE-mediated reactions to local anesthetics are rare. Here we report a 44 year-old female who demonstrated in vivo and in vitro IgE-mediated reactions to both amide and ester anesthetics.
Methods: Percutaneous and intradermal skin testing followed by a graded injection challenge was performed. ELISA was performed on the patient's serum with local anesthetics from the amide and ester classes, latex, metabisulfite, and methylparabens.
Results: Intradermal skin testing was positive to a 1:10 dilution of 1% tetracaine. A graded injection challenge to both 1% lidocaine and 4% articaine was positive with generalized pruritis and hives. The patient demonstrated positive ELISA results for lidocaine, articaine, mepivacaine, bupivacaine, procaine, and tetracaine; metabisulfite and methylparabens were negative on ELISA. A basophil histamine release assay for lidocaine was negative. Latex skin testing, serum latex IgE, and a latex glove use test were negative.
Conclusions: This is the first case report to demonstrate in vitro IgE binding within a single patient to both amide and ester anesthetics. Although the patient had a positive challenge to local anesthetics, demonstration of IgE varied between different methodologies.

Arerugi. 2009 Jun;58(6):657-64.
[Clinical examination of challenge test to local anesthetics].
[Article in Japanese]
Yamaguchi T, Nakagome K, Udagawa K, Takaku Y, Sato N, Soma T, Hagiwara K, Kanazawa M, Nagata M.
Source
Department of Respiratory Medicine, Saitama Medical University.
Abstract
Background: Although adverse reactions to local anesthetics are often diagnosed as local anesthetic allergy, there is evidence that most of these reactions occur via non-allergic mechanisms.
Methods: To evaluate allergic reactions to local anesthetics, challenge tests were performed in 20 patients who had a history of adverse events to local anesthetics for whom dental treatment was planned. The diagnostic protocol of this challenge test consisted of skin prick and intracutaneous tests, as well as subsequent incremental subcutaneous challenge tests with local anesthetics such as lidocaine.
Results: 17 patients (85%) showed no immediate allergic response to lidocaine, which could then be used for dental treatment. Three patients (15%) reacted positively to lidocaine: one had local erythema at the site of the skin prick, and two reacted to subcutaneous challenge.
Conclusion: The proportion of immediate-type reactions to local anesthetics is small but not rare in patients suspected of having local anesthetic allergy. This result suggests that the diagnostic approach to confirm allergy to local anesthetics is clinically important and requires further study in a larger population.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology