Immediate local anesthetic reactions and diagnostic test results in pediatric patients.

BACKGROUND/OBJECTIVES: Adverse reactions to local anesthetics are relatively common, but proven IgE-mediated allergy is extremely rare. We aimed to determine the frequency of local anesthetic allergy in pediatric patients. PATIENTS AND METHODS: The medical records of 73 patients who presented to our clinic with a history of suspected allergic reaction to local anesthetics and underwent diagnostic testing between 2012 and 2020 were retrospectively analyzed. Diagnoses were based on case histories, skin tests, and subcutaneous challenge tests. RESULTS: A total of 75 test series were carried out on the 73 patients (43 boys; median [IQR] age 9.25 [7.26-14.25] years, range 3-17.8 years). The most commonly tested drugs were lidocaine (n = 38; 50.6%) and prilocaine (n = 15; 20%). Local anesthetic allergy was confirmed in one (1.3%) of the 73 patients by positive subcutaneous challenge test with mepivacaine. CONCLUSION: There are limited data in the current literature regarding local anesthetic allergies and diagnosis test results in pediatric patients. Proven local anesthetic allergy is less common than expected by society and physicians, and therefore diagnostic tests are needed for patients with no contra-indications such as severe or life-threatening reactions.

Local anesthetics allergy: who should be tested?

Summary: Objective. To document the test results of patients referred to our clinic for testing with local anesthetics (LAs) in real life conditions and provide data related to the necessity of these tests. Methods. All consecutive subjects who were referred to be evaluated for LA allergy during a two-year follow up were included in the analysis. All subjects underwent skin prick / intradermal tests followed by a subcutaneous provocation test with the LAs tested. Results. A total of 228 subjects were included. The main referral reason was the presence of a history of drug hypersensitivity reaction (DHR) to drugs other than LAs (n = 128; 56%), whereas a history of LA allergy constituted the second most common referral reason (n = 64, 28.1%). In the majority of cases (n = 39; 60.9%), the culprit LA was not known by the patients. Asthma was the third most common referral reason, presented in 49 cases (21.5%). Ten cases had positivity to the tested LA in skin testing / challenges. Nine out of 10 patients had a history of DHR to drugs other than LA, whereas 5 of them had also a history of DHR to LA. Six of the 10 patients had a history of multiple DHR. None of the asthma patients without any DHR history were positive in the LA tests. Eight out of 10 cases who underwent skin testing / challenge with an alternative LA, tolerated the alternative LA. Conclusion. The most common referral reason for testing with LA was a history of DHR to drugs other than LAs, whereas asthma was the third most common referral reason. Patients with a history of multiple DHR may be considered for testing with LAs. Asthmatics and those with other allergic diseases without a history of drug / LA allergy do not need to be tested with LA.

Positive relationship-intensity of response to p-phenylenediamine on patch testing and cross-reactions with related allergens.

BACKGROUND: Hair dye exposure is the most common cause of sensitization to p-phenylenediamine (PPD). Cross-reactions with structurally related allergens occur. OBJECTIVES: It is suggested that a stronger patch test reaction (3+ rather than 1+) to PPD (usually tested as 1% petrolatum) is associated with an increased propensity for cross-reactions. In this article we will demonstrate this association. METHODS: Of 230 patients with allergic reactions to PPD on patch testing identified during 2007-2012 from clinical records, notes for 221 were available for review. Data were collected regarding age, sex, and grade of reaction [International Contact Dermatitis Research Group (ICDRG) criteria] to PPD. Cross-reactions with the following allergens, found in our baseline series, were recorded: Disperse Yellow 3, N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), and caine mix. Having excluded 23 doubtful reactions, the reactions from 198 patients were further considered. RESULTS: Of the patients, 75.3% (n = 149) were female, and the mean age was 48.6 years (12-82 years). Of the patients allergic to PPD, 16.6% (n = 33) showed cross-reactions with one or more related allergens. Cross-reactions were seen in 16% with a grade of 1+, 14.5% with a grade of 2+, 28.6% with a grade of 3+ when PPD was tested 1% pet., and 50.0% when PPD was tested at 0.1-0.001%, arbitrarily considered to be 4+ (p = 0.02; Cramér's V = 0.23). CONCLUSION: An increasing likelihood of reactions to Disperse Yellow 3, IPPD or caine mix was seen with increasing strength of patch test reaction to PPD. The clinical relevance of these cross-reactions is unclear.

The negative predictive value of typing safe local anesthetics.

BACKGROUND: Although allergy to local anesthetics (LA) is rare, patients often report unwanted reactions after their administration. A history of anaphylaxis or an atypical reaction related to LA is an indication for typing a safe anesthetic for future surgical or dental procedures. AIM: The aim of the study was to determine the negative predictive value (NPV) of typing safe LA. METHODS: A total of 154 patients with a history of an unwanted reaction to LA were enrolled into the study. Stepwise typing of a safe anesthetic included skin prick tests (SPT) and intracutaneous tests (ICT) with two or three of the following LA: lidocaine, bupivacaine, mepivacaine, and articaine. Skin tests were followed by provocations with one or two LA. Telephone follow-up visits were performed 4-12 months after drug typing. On the basis of follow-up questionnaire results, the NPV of the protocol was calculated. RESULTS: The full protocol was performed in 148 patients. Positive results of SPT were observed in 2, of ICT in 19 and of provocations in 11 cases. Lidocaine was found safe in 44, bupivacaine in 14, mepivacaine in 34 and articaine in 61 patients. The drug typed at the clinical visit was administered in 78 patients, and 76 reported no reactions (NPV = 97%). CONCLUSION: Stepwise approach including SPT, ICT and provocations is safe and allows typing a safe anesthetic in a vast majority of patients.

IgE-mediated allergy to local anaesthetics: separating fact from perception: a UK perspective.

Local anaesthetic (LA) agents have been routinely used in dentistry, ophthalmology, minor surgery, and obstetrics since the late nineteenth century. Reports relating to adverse reactions and LA allergy have appeared in the published literature for several years. However, the incidence of true, IgE-mediated LA allergy remains uncertain and is presumed to be very low. We critically reviewed the English language literature on suspected LA allergy and its investigation with the aim of estimating the reported prevalence and analysing the role of different tests currently used to identify and confirm LA allergy. Twenty-three case series involving 2978 patients were identified and analysed. Twenty-nine of these patients had true IgE-mediated allergy to LA, thus confirming the reported prevalence of LA allergy in large series to be <1% (0.97%). The protocols used in the investigation of these patients have also been discussed. Evidence from this review confirms the rarity of IgE-mediated allergy to LA and supports an investigation strategy based on using the clinical history to select patients for skin testing and challenge. We believe that such a triage process would alleviate pressures on allergy services without compromising patient safety.

Cocaine Allergy in Drug-Dependent Patients and Allergic People.

BACKGROUND: Adverse reactions to local anesthetics (LAs), especially esters, are not uncommon, but true allergy is rarely diagnosed. To our knowledge, currently there is no reliable method of determining IgE-mediated hypersensitivity to LAs and cocaine. OBJECTIVE: To assess the clinical value of allergy tests (prick, IgE, challenges, and arrays) in people suffering hypersensitivity reactions (asthma and anaphylaxis) during local anesthesia with cocaine derivatives and drug abusers with allergic symptoms after cocaine inhalation. METHODS: We selected cocaine-dependent patients and allergic patients who suffered severe reactions during local anesthesia from a database of 23,873 patients. The diagnostic yield (sensitivity, specificity, and predictive value) of allergy tests using cocaine and coca leaf extracts in determining cocaine allergy was assessed, taking a positive challenge as the criterion standard. RESULTS: After prick tests, specific IgE, and challenge with cocaine extract, 41 of 211 patients (19.4%) were diagnosed as sensitized to cocaine. Prick tests and IgE to coca leaves (coca tea) had a good sensitivity (95.1% and 92.7%, respectively) and specificity (92.3 and 98.8%, respectively) for the diagnosis of cocaine allergy and LA-derived allergy. CONCLUSIONS: Cocaine may be an important allergen. Drug abusers and patients sensitized to local anesthesia and tobacco are at risk. Both prick tests and specific IgE against coca leaf extract detected sensitization to cocaine. The highest levels were related to severe clinical profiles.

Twenty Years' Experience with Anaphylaxis-Like Reactions to Local Anesthetics: Genuine Allergy is Rare.

BACKGROUND: Anaphylaxis-like reactions occur within minutes after the application of local anesthetics (LA), most commonly during dental interventions. Impressive symptoms including respiratory distress or loss of consciousness frequently give rise to a suspicion of allergy and may prompt patients and treating physicians to refuse future LA injections. OBJECTIVE: Nonallergic mechanisms are responsible for the majority of LA-induced immediate-type reactions. In view of the preponderance of nonallergic reactions, the question arises whether genuine LA allergy may be missed during routine testing procedures. METHODS: We retrospectively evaluated clinical data and test results from patients referred to our allergy clinic within the past 20 years for diagnostic workup of LA-induced immediate-type reactions. RESULTS: Of 402 evaluated patients, 29 had an episode of acute urticaria within 30 minutes after LA injections, and the remaining 373 had a history of mainly subjective cutaneous, respiratory, cardiovascular, and neurological complaints. Of the patients reporting urticaria with or without angioedema, 14 were diagnosed with a spontaneous episode of urticaria, 13 had allergic or nonallergic reactions to other agents, and 2 had IgE-mediated LA allergy. LA allergy was definitely excluded by 771 subcutaneous provocation tests with skin test negative LA, thereby demonstrating the high predictive value of negative intradermal testing. CONCLUSIONS: Skin testing and provocative LA challenge are useful to exclude LA allergy, and this testing procedure seems to be appropriate to identify the extremely rare cases with IgE-mediated LA allergy.

A critical review of local anesthetic sensitivity.

With their ability to block pain signals to the brain, local anesthetics (LAs) have made possible many surgical procedures and interventions once thought impossible. LAs are generally safe and well tolerated when used correctly by trained professionals. However, adverse reactions do occur, and may generate a referral to an Allergist for evaluation of LA allergy. LA structure, classification, and metabolism will be briefly reviewed. A critical analysis of the studies and case reports involving LA allergy found via PubMed search for "local anesthetic allergy" and "local anesthetic hypersensitivity" will be discussed. In addition, the clinical evaluation of a patient with concern for a LA allergy will be examined.

Approach to patients with suspected hypersensitivity to local anesthetics.

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.

The Importance of Prolonged Provocation in Drug Allergy - Results From a Danish Allergy Clinic.

BACKGROUND: Drug provocation is the "Gold Standard" in drug allergy investigation. Recent studies suggest that a negative drug provocation on first dose should be followed by a prolonged provocation over several days. OBJECTIVE: To evaluate drug allergy investigations on the basis of drug provocation, including prolonged provocation. METHODS: Data from adult patients investigated for drug allergy in a Danish Allergy Clinic during the period 2010 to 2014 were entered into a database. Data included clinical details and results of provocations with suspected culprit drug (for penicillins performed only in specific IgE-negative patients). If provocation was negative on first dose, treatment was continued for 3 to 10 days. RESULTS: A total of 1,913 provocations were done in 1,659 patients, median age 46 years, of whom 1,237 (74.6%) were females. Drugs investigated were antibiotics, 1,776 (92.8%), of which 1,590 (89.5%) were penicillins; analgesics, 59 (3.1%); local anesthetics, 33 (1.7%); and other drugs, 45 (2.4%). In total, 211 of 1,913 (11.0%) provocations were positive. Causes were antibiotics, 198 (93.8%), of which 167 (84.3%) were penicillins; analgesics, 7 (3.3%); local anesthetics, 0; and other drugs, 6 (2.8%). Only 43 (20.4%) provocations were positive on first dose, whereas 95 (45.0%) turned positive more than 3 days later. CONCLUSIONS: Only 11.0% of the provocations were positive. Importantly, only 1 of 5 patients tested positive on the first dose, indicating that prolonged exposure should always be considered when drug provocation is included in allergy investigations. Most provocations were with penicillins, reflecting the pattern of antibiotic use in Denmark, which differs from that in other countries, especially outside Northern Europe.

Cross-reactivity among amide-type local anesthetics in a case of allergy to mepivacaine.

Among the various adverse reactions to local anesthetics, IgE-mediated reactions, particularly to the more commonly used amide group, are extremely rare. We report the case of a 39-year-old man who suffered itching and generalized urticaria with facial angioedema 15 minutes after administration of mepivacaine. Skin tests revealed a strong positive reaction to mepivacaine, lidocaine, and ropivacaine, but negative reactions to bupivacaine and levobupivacaine. Furthermore, double-blind placebo-controlled subcutaneous challenge with bupivacaine and levobupivacaine was well tolerated. We conclude that an extensive allergologic study must be carried out in rare cases of true allergic reaction to amide-type local anesthetics in order to rule out cross reactivity.

Prevalence of drug allergy in an out-patient population.

The prevalence of drug allergy in an out-patient population has been studied, 448 cases were diagnosed mainly to NSAIDS and beta-lactams and local anesthetics, sulfa drugs, quinolones and others. Clinical history and skin tests are sufficient to diagnose most cases of drug allergy.

Recognition of local anesthetics by alphabeta+ T cells.

Patients with drug allergy show a specific immune response to drugs. Chemically nonreactive drugs like, for example, local anesthetics are directly recognized by alphabeta+ T cells in an HLA-DR restricted way, as neither drug metabolism nor protein processing is required for T cell stimulation. In this study we identified some of the structural requirements that determine cross-reactivity of T cells to local anesthetics, with the aim to improve the molecular basis for the selection of alternatives in individuals sensitized to a certain local anesthetic and to better understand presentation and T cell recognition of these drugs. Fifty-five clones (52 lidocaine specific, three mepivacaine specific from two allergic donors) were analyzed. Stimulatory compounds induced a down-regulation of the T cell receptor, demonstrating that these non-peptide antigens are recognized by the T cell receptor itself. A consistent cross-reactivity between lidocaine and mepivacaine was found, as all except one lidocaine specific clone proliferated to both drugs tested. Sixteen chemically related local anesthetics (including ester local anesthetics, OH- and desalkylated metabolites) were used to identify structural requirements for T cell recognition. Each of the four clones examined in detail was uniquely sensitive to changes in the structures of the local anesthetic: clone SFT24, i.e., did not recognize any of the tested OH- or desalkylated metabolites, while the clone OFB2 proliferated to all OH-metabolites and other differently modified molecules. The broadly reactive clone OFB2 allowed us to propose a model, suggesting that the structure of the amine side chain of local anesthetics is essential for recognition by the T cell receptor.

Cross-reactivity with drugs at the T cell level.

PURPOSE OF REVIEW: Cross-reactivity with drugs is an important clinical problem in drug hypersensitivity. Once a patient is labeled 'drug-allergic' all drugs of the same class are withheld and future therapeutic interventions are limited. Here we review cross-reactivity with drugs at the T cell level. RECENT FINDINGS: Analysis of T cell recognition of various classes of drugs (beta-lactam antibiotics, sulfonamides, local anesthetics) using T cell clones suggests that at the T cell level the whole structure, in particular the core and to a lesser degree side chains, are recognized. SUMMARY: It is necessary to differentiate cross-reactivity mediated by T cells and antibodies as only the latter seem to recognize side chains exclusively.

Fixed drug eruption induced by lidocaine and patch testing.

Fixed drug eruption (FDE) is a peculiar drug-induced cutaneous reaction, that characteristically reappears at the same site when the etiologic drug is readministered. We present a case of a 27-year old male who was referred to us after two episodes of erythema on the palms, soles, and genital areas with posterior desquamation after receiving local anesthetics. Skin tests with lidocaine, mepivacaine and bupivacaine were negative. Eight hours after challenge with lidocaine the lesions reoccurred. Patch tests with lidocaine on healthy skin and residual lesions were negative, but 48 hours later the lesions reappeared on the same areas as before. Challenge with mepivacaine and bupivacaine were negative.

[Internal medicine and local anesthesia in dentistry. A review of possible side effects]. / Inwendige geneeskunde en lokale anesthesie in de tandheelkunde. Een overzicht van mogelijke bijwerkingen.

When using local anaesthesia the dentist may be confronted with a variety of side effects, either caused by the anaesthetic solution itself or its additives, including vasoconstrictive drugs such as epinephrine. Early recognition and treatment of these side-effects are essential. Even more important is the possible prevention of such side-effects by a properly taken medical history before using local anaesthesia.

[Allergic reactions to local anesthetics]. / Allergische reacties op lokale anaesthetica.

In this article type I and type IV allergic reactions evoked by local anaesthetics are discussed. Contact dermatitis (type IV) reactions are mainly caused by local anaesthetics of the ester-type like procaine. Both contact dermatitis and anaphylactic reactions (type I) can be caused by anaesthetics of the amide-type (e.g. lidocaine), but these reactions are rare. Intra- and epicutaneous tests can be useful to prove allergy, but sometimes provocation tests are necessary. Many reactions are not caused by an allergic mechanism.