Evaluation of adverse reactions to local anesthetics: experience with 236 patients.

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.     

IgE-mediated adverse reactivity to a radiographic contrast medium.

In a patient with a previous history of a serious reaction after intravenous injection of the cholangiographic agent ioglycamic acid (Bilivistan), intravenous cholangiography appeared to be necessary. Therefore intradermal tests were performed in the patient and four controls with three radiographic contrast media closely related in chemical structure. In addition a Prausnitz-Kustner test with heated and unheated patient serum was performed. These tests demonstrated the presence in this patient of selective immediate-type reactivity to ioglycamic acid which was probably IgE mediated. Intravenous cholangiography with iodipamide seemed justified and resulted in no adverse reactions. Although this case may be exceptional, the results suggest that intradermal skin tests at proper concentrations may be useful in choosing the administration of radiographic contrast medium to patients with a history of prior adverse reactions.     

T-cell reaction to local anaesthetics: relationship to angioedema and urticaria after subcutaneous application — patch testing and LTT in patients with adverse reaction to local anaesthetics

BACKGROUND: Local anaesthetics are known to elicit T-cell reactions after epicutaneous application, namely contact dermatitis. In addition, adverse reactions like urticaria and angioedema are rather common after submucosal or subcutaneous injection. The pathogenesis of these side-effects, which appear frequently hours after application, is unknown, but thought to be not immunoglobulin E-mediated, since immediate skin tests are mostly negative. OBJECTIVES: We investigated whether patients who developed urticaria and angioedema after subcutaneous application have a T-cell sensitization to local anaesthetics, which might be responsible for the symptoms. METHODS: Twenty patients with generalized and/or local cutaneous reactions after LA were examined with intradermal testing using a standard panel of six LAs and patch testing using between seven and nine LAs in vaseline and four LAs in PBS. In 10 patients, a lymphocyte transformation test (LTT) was performed. RESULTS: Only 2/20 patients had an immediate skin reaction (positive intradermal test), whereas 6/20 patients had a positive delayed skin reaction (positive patch test). In 6/10 subjects the LTT was positive. CONCLUSIONS: Delayed appearance of urticaria and angioedema after subcutaneous application of local anaesthetics may be related to a T cell- mediated sensitization, which might be detected by patch testing or LTT.     

Delayed-type hypersensitivity to subcutaneous enoxaparin

Background Enoxaparin and other low-molecular-weight heparins are widely used to prevent and treat thromboembolic disorders. Cutaneous reactions secondary to enoxaparin injections include delayed hypersensitivity skin reactions described as erythematous, infiltrated plaques at injection sites. We studied three cases of erythematous infiltrated plaques after enoxaparin injection in order to establish the allergenic importance of this low-molecular-weight heparin.
Methods Patch tests were performed with sodium heparin, calcium heparin, calcium enoxaparin, and calcium nadroparin, A subcutaneous test with calcium heparin and an intravenous challenge test with sodium heparin were done, A punch biopsy was obtained from an erythematous plaque in one patient.
Results Patch tests were negative to calcium heparin in all patients, positive t o enoxaparin and nadroparin in two patients, and positive to sodium heparin i n one patient. In two patients, the subcutaneous challenge test was positive, the intravenous challenge test was negative, and the histopathologic appearance of the biopsy resembled a delayed-type hypersensitivity reaction. Conclusions TTiese cases provide evidence of type IV hypersensitivity and the possibility of crossed-allergenicity among unfractionated heparin and low-molecular-weight heparins. We show that the subcutaneous challenge test is the most reliable diagnostic measure.     

Usefulness of intradermal test and patch test in the diagnosis of nonimmediate reactions to metamizol

BACKGROUND: Metamizole is a pyrazolone derivative, and its most common reactions are IgE-mediated reaction and idiosyncratic reactions. Non-immediate reactions are poorly described and there are very few reports on non-immediate reactions to pyrazolones. MATERIALS AND METHODS: We evaluated 12 patients (nine men) who consulted for a non-immediate reaction after metamizol administration. We performed cutaneous tests (skin prick tests and immediate and delayed intradermal tests) and epicutaneous tests, and, if necessary, an oral challenge test. RESULTS: All skin prick and intradermal tests, if necessary, were negative in immediate reading. Delayed intradermal tests were positive in six of 10 patients (60%) and epicutaneous tests were positive in four of 11 patients (36%). Three cases (25%), were diagnosed by a positive oral challenge test. DISCUSSION: Delayed-reading intradermal tests and patch tests are useful tools in the diagnosis of nonimmediate reactions to pyrazolones and should be considered the first step when evaluating these type of reactions. Intradermal test appears to be more sensitive than patch test. The positivity of skin tests suggests an immunological reaction, probably mediated by T lymphocytes, but further studies are required.     

Anaphylaxis caused by benzalkonium in a nebulizer solution

Benzalkonium chloride (BAC) is commonly used as a bactericidal preservative in nebulizer solutions, and can cause paradoxical onchoconstriction following nebulizing therapy in some asthmatics. We describe a case of anaphylactic shock in a 23-yr-old asthmatic woman following an intradermal skin test with a salbutamol solution containing BAC. Since she complained of cough and dyspnea after inhalation therapy with a nebulizer solution, we conducted an intradermal skin test using the same solution, which contained BAC. About 10 min later, the patient reported dizziness, palpitations, and dyspnea. On examination, tachycardia, tachypnea, and hypotension were found. She was resuscitated with a subcutaneous injection of epinephrine and an infusion of saline. One month later, we conducted a bronchial provocation test with BAC, and she showed a positive response.     

Human hypersensitivity to a sham vaccine prepared from mosquito-cell culture fluids

A sham vaccine, prepared with the C6/36 cell line derived from larval Aedes albopictus mosquitoes, was skin tested on 12 volunteers. Although no reactions were observed after prick tests, three immediate reactions did occur after intradermal tests. Subcutaneous administration of the C6/36 sham vaccine was initially performed on the nine subjects who did not demonstrate immediate reactions. Five of these subjects developed delayed reactions at the site of the intradermal test within 12 hr after inoculation. A Prausnitz-Küstner test was performed on the back of one unsensitized subject by use of both unheated and heated sera from three subjects who had immediate skin reactions, three who demonstrated a delayed reaction, and one who had a negative skin response. In the Prausnitz-Küstner test, immediate skin reactions were observed with all seven unheated sera but with none of the heated serum aliquots. The determination that skin reactivity was associated with a heat-labile serum factor suggested the mechanism was IgE-mediated. Under close surveillance, the C6/36 sham vaccine was administered subcutaneously to one volunteer who had previously demonstrated an immediate response. This subject developed an anaphylactic reaction characterized by hives at the site and more distantly from the site of the subcutaneous inoculation. Hypersensitivity to A. albopictus larval antigens is common and precludes the use of C6/36 cell culture as a substrate for viral vaccines.     

Administration of local anesthetics to patients with a history of prior adverse reaction

The clinical histories of 71 patients evaluated for suspected local anesthetic (LA) allergy were reviewed retrospectively. The clinical histories were classified into (1) immediate generalized reactions (15%), (2) localized swelling at the injection site (25%), (3) nonspecific systemic symptoms (42%), and (4) other histories (17%). Serial dilutional intradermal skin tests were performed with mepivacaine, lidocaine, and procaine in 59 patients. There were 5 skin test--positive patients found, and each had a positive reaction to an LA to which, by history, they had not reacted. In 50 patients, when an LA was subsequently required, a subcutaneous challenge was performed with an LA chosen for chemical nonsimilarity. No significant reactions were observed in this group. Three patients tolerated a challenge with an LA to which they were skin test--positive. These data indicate (1) the low incidence of reactions compatible with a systemic IgE-mediated mechanism by history in patients referred for evaluation of LA allergy, (2) the lack of specific and clinically relevant information provided by dilutional skin tests, and (3) the apparent safety and usefulness of careful challenge with an alternative LA.     

Aluminium-induced granulomas after inaccurate intradermal hyposensitization injections of aluminium-adsorbed depot preparations

BACKGROUND: The development of persistent subcutaneous nodules at the injection sites of aluminium-adsorbed hyposensitization solutions is rare. These nodules have been interpreted as a delayed, granulomatous hypersensitivity reaction to aluminium. We report for the first time a case of persistent intradermal granulomas that developed at the sites of inaccurate intradermal, instead of subcutaneous, hyposensitization injections. METHODS: An intradermal nodule was excised and processed for histopathology, scanning electron microscopy, and X-ray microanalysis. Intradermal and patch tests with aluminium hydroxide were performed. RESULTS: Histologically, the nodule presented a pattern of granulomatous inflammatory reaction surrounding foci of necrotic tissue. Scanning electron microscopy and X-ray microanalysis revealed deposits of aluminium within the granulomas. Patch tests with aluminium hydroxide were negative, and intradermal tests caused persistent intradermal granulomas. Subsequent hyposensitization therapy in our department with the usual subcutaneous injections of aluminium-adsorbed allergen extracts was well tolerated by the patient. CONCLUSIONS: Local toxic effects of aluminium may be crucial in the development of persistent intradermal injection-site granulomas. Such intradermal nodules may develop even if the subcutaneous route is well tolerated. We conclude that inaccurate intradermal injections of aluminium-containing solutions have to be strictly avoided.     

Systemic reactions to allergy skin tests.

BACKGROUND: Skin testing is a common diagnostic tool in allergy. It is considered a safe procedure, although systemic reactions have been reported. OBJECTIVE: To identify the systemic reaction rates of allergy skin tests and to determine the clinical outcome of such reactions. METHOD: This retrospective study used a computerized database at the Mayo Clinic to identify patients who developed systemic reactions to skin tests. Altogether 497,656 skin tests were performed on 18,311 patients from January 1992 to June 1997. Skin puncture tests were performed on 16,505 patients. Skin puncture and intradermal skin tests were performed on 1,806 patients. Systemic reactions were evaluated and treated by physicians. RESULTS: There were 6 systemic reactions, an overall rate of 33 systemic reactions per 100,000 skin tests. All six patients had asthma. The systemic reaction rates for latex skin testing was 152 or 228 reactions per 100,000 latex skin tests, to penicillin and antibiotics 72 reactions per 100,000 penicillin and antibiotics skin tests, and to aeroallergens 15 or 23 reactions per 100,000 aeroallergen skin tests. The systemic reaction rate for skin puncture test was 30 reactions per 100,000 skin puncture tests, for skin puncture and intradermal skin tests, the rate was 55 reactions per 100,000 skin puncture and intradermal skin tests. All 6 patients were treated and dismissed within 1 hour after treatment. CONCLUSION: The systemic reaction rate to skin tests was very low. Systemic reactions were mild and all patients recovered fully within 1 hour.     

Studies on antibiotic skin testing

Commercially available antibiotics for injection are supplied with test ampules. Users are instructed to dissolve them to make 300 micrograms/ml solution for intradermal pretests to avoid allergic reactions. Sometimes this concentration is too low to prevent anaphylactic reactions. In the present study, we tried to find the maximum concentration for the intradermal tests which would have high sensitivity without giving nonspecific, false positive reactions. We investigated intradermal tests with cephalothin (CET) in a patient who suffered from anaphylaxis after drip infusion with CET, although she was judged to be negative to CET by the usual intradermal test prior to the infusion. Her CET skin test was negative at a concentration of 150 micrograms/ml and positive at 300 micrograms/ml 6 weeks after anaphylaxis, but negative at 300 micrograms/ml and positive at 1000 micrograms/ml 4 and 7 years after anaphylaxis. Prick tests were always negative, even with the maximum soluble concentration of CET, 200 mg/ml. Nonspecific reactions to intradermal tests at concentrations as high as 1000 micrograms/ml were examined with 20 kinds of penicillins and cephems in 51 healthy subjects without histories of drug allergies. Very few false positive reactions were observed, except in 5 out of 24 cases with cefotiam. Intradermal tests at 3000 micrograms/ml, however, frequently resulted in nonspecific reactions. We conclude that 1000 micrograms/ml, not 300 micrograms/ml solutions should be used for intradermal tests to prevent allergic reactions to the injection of antibiotics.     

Oral muscle relaxant may induce immediate allergic reactions

Eperisone and afloqualone act by relaxing both skeletal and vascular smooth muscles to improve circulation and suppress pain reflex. These drugs are typically prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) as painkillers. However, there have been no reports on serious adverse reactions to oral muscle relaxants; and this is the first report to describe three allergic reactions caused by eperisone and afloqualone. All three patients had histories of allergic reactions after oral intake of multiple painkillers, including oral muscle relaxants and NSAIDs, for chronic muscle pain. An open-label oral challenge test was performed with each drug to confirm which drugs caused the systemic reactions. All patients experienced the same reactions within one hour after oral intake of eperisone or afloqualone. The severity of these reactions ranged from laryngeal edema to hypotension. To confirm that the systemic reaction was caused by eperisone or afloqualone, skin prick testing and intradermal skin tests were performed with eperisone or afloqualone extract in vivo, and basophil activity tests were performed after stimulation with these drugs in vitro. In one patient with laryngeal edema, the intradermal test with afloqualone extract had a positive result, and CD63 expression levels on basophils increased in a dose-dependent manner by stimulation with afloqualone. We report three allergic reactions caused by oral muscle relaxants that might be mediated by non-immunoglobulin E-mediated responses. Since oral muscle relaxants such as eperisone and afloqualone are commonly prescribed for chronic muscle pain and can induce severe allergic reactions, we should prescribe them carefully.     

Long-term evaluation of usefulness of skin and incremental challenge tests in patients with history of adverse reaction to local anesthetics

A variety of adverse reactions to local anesthetics has been described, some of which are thought to be allergic. Different protocols of prick and intradermal skin tests as well as subcutaneous challenge tests are used to select a local anesthetic which can safely be used. Their long-term effectiveness has not yet been assessed. Twenty-eight patients with a history of adverse reaction to local anesthetics were evaluated over a 3-year period. Loss of consciousness occurred in eight patients, skin reaction in nine, and vagal symptoms in eight. Various reactions were recorded in the remaining three patients. Rapid spontaneous recovery was the rule, suggesting that immediate allergic reaction and, in particular, anaphylactic reaction were unlikely. Investigation allowed the selection of a tolerated anesthetic in all cases. Reexposure occurred in 19 patients 16–50 months after evaluation and 6.8 ± 5.5 years after the first reaction. No patient presented a second reaction. In conclusion, adverse reactions to local anesthetics seem to be, in most cases, not allergic in nature. Evaluation protocols are effective in selecting an agent susceptible to tolerance, but are time consuming. However, they probably contribute to an important reassurance effect that is likely to increase tolerance to subsequent local anesthetic administration. Simplification of the protocols and better patient selection are proposed.     

A diagnostic protocol for evaluating nonimmediate reactions to aminopenicillins

BACKGROUND: Maculopapular and urticarial rashes are nonimmediate manifestations common during aminopenicillin (AP) treatment, and the former often represent cell-mediated hypersensitivity. OBJECTIVES: We sought to determine the significance and incidence of skin test reactions to APs in adults reporting adverse reactions during therapy with these beta-lactams and, particularly, to evaluate the potential of patch tests, delayed-reading skin tests, and challenges in the diagnosis of nonimmediate reactions. METHODS: We used skin tests with penicilloylpolylysine, minor determinant mixture, benzylpenicillin, ampicillin, and amoxicillin, as well as patch tests with the last 3 drugs. We also performed in vitro assays for specific IgE and challenges with the suspect penicillin in subjects with nonimmediate reactions. RESULTS: Among the 144 patients reporting nonimmediate manifestations (mostly maculopapular rashes), delayed hypersensitivity was diagnosed in 62 on the basis of positive patch test and/or delayed intradermal test results and responses to challenges; negative reactions to challenges allowed us to reasonably exclude the possibility of allergy in 66 subjects, and the challenge confirmed that 1 patient had linear IgA bullous dermatosis. Definitive diagnoses could not be provided for the remaining 15 subjects, who had negative allergologic test results, because they did not consent to challenges. In 40 of 49 immediate reactors, a diagnosis of IgE-mediated hypersensitivity was made. CONCLUSIONS: Both patch and intradermal tests are useful in evaluating nonimmediate reactions to APs. Positive patch test and delayed intradermal responses together indicate delayed hypersensitivity. Intradermal testing appears to be more sensitive than patch testing, but the pattern of positive delayed intradermal test responses and negative patch test responses needs further investigation because of false-positive cases.     

Anaphylaxis to diclofenac: nine cases reported to the Allergy Vigilance Network in France

Nine cases of diclofenac hypersensitivity recorded by the Allergy Vigilance Network in France from 2002 to 2012 were studied. Data from history, symptoms, skin tests, basophil activation tests, and oral challenge (OC) were recorded. Grade 3 severe anaphylactic reactions occurred in seven cases of nine. IgE‐dependent anaphylaxis was confirmed in six cases: positive intradermal tests (n = 4), a syndromic reaction during skin tests (n = 1), and one case with grade 1 reaction and negative skin tests had an anaphylactic shock to the OC. A nonimmune reaction was suspected in one case. An IgE‐dependent mechanism may be the predominant cause of adverse reactions to diclofenac. Allergy skin tests must be carried out sequentially at the recommended concentrations. BATs may be helpful because they can support the diagnosis of anaphylaxis. Given the risks of a direct challenge to diclofenac, OC to aspirin should be performed first to exclude a nonimmunologic hypersensitivity to NSAIDs. Tests for specific IgEs to most frequently used NSAIDs such as diclofenac and ibuprofen are urgently needed.     

Skin testing in patients with hypersensitivity reactions to iodinated contrast media – a European multicenter study

Background:  Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions.
Methods:  Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls.
Results:  Skin test specificity was 96–100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure.
Conclusions:  These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors.     

Isolated late cutaneous reactions to allergen skin testing in children.

BACKGROUND: Occasionally parents report a reaction developing at the site of an allergen skin test several hours after application of the test, despite there having been no immediate reaction. The medical literature contains little information regarding isolated late reactions (ILRs) to allergen skin testing. OBJECTIVE: The goal of this project was to determine the incidence of ILRs in children undergoing allergen skin testing. METHODS: Prick and intradermal (ID) skin testing was performed for routine clinical indications in an allergy clinic. Children with a positive histamine control, and at least one negative immediate reaction to allergen skin testing were enrolled in the study. The parents were given detailed instructions to examine the skin test sites 6 hours later, and to record the size of any erythematous indurated sites. Circles of various diameters were included on the report form to assist the parents' size estimates. RESULTS: Fifty-seven children enrolled in the study and 50 returned the forms. No patients reported ILRs to prick skin tests. Eighteen of the 50 respondents reported 40 ILRs to ID tests, of > or = 5 mm diameter; 7 of these were > or = 10 mm. The most common allergen causing ILR was cockroach, accounting for 20% of the ILRs. Each of the other allergens also caused ILRs. The clinical history did not show a definite correlation of symptoms with exposure to the allergens causing ILRs, although all 14 patients with ILRs to indoor allergens had year-round symptoms. There was no correlation between the incidence of ILRs and age, gender, or diagnosis of asthma. CONCLUSION: ILRs to allergen skin testing occurred in 36% of pediatric allergy clinic patients. The clinical significance of such reactions is unknown.     

Studies on the effect of systemic administration of sensitizers to guinea-pigs with contact sensitivity to inorganic metal compounds: V. Studies on the mechanism of the `flare up'' reaction

The mechanism of the `flare up' reaction of previous epicutaneous skin test sites in guinea-pigs sensitized to potassium dichromate seems to be similar to that of the Arthus phenomenon and different from that of contact skin sensitivity.

No circulating antibodies were found in the serum of these animals but it was possible to transfer the capacity of developing `flare up' reactions by an intradermal injection of peritoneal exudate cells from sensitized donors to normal recipients in which a `flare up' could be elicited by intravenously injecting the hapten 4 days later.

`Flare up' reactions could also be transferred by cells from animals permanently desensitized to contact hypersensitivity to chromium. This is in agreement with the ability to produce `flare up' reactions in desensitized animals.

The assumption that the `flare up' reaction is produced by humoral antibodies released by sensitized lymphocytes in the skin test site is further supported by the finding of an activity in the supernatant of cultures of sensitized lymphocytes with a chromium conjugated guinea-pig serum which when injected intradermally into normal recipients can produce an Arthus-like reaction.

     

Long-term absence of sensitization to mepivacaine as assessed by a diagnostic protocol including patch testing

BACKGROUND: Prospective assessment of non-reactivity to local anaesthetics is a frequent reason for allergy consultation. OBJECTIVES: To investigate the clinical profiles of subjects referred for allergy evaluation; to prospectively reduce the frequency of evaluation by assessing the persistence, during clinical use, of non-reactivity to contaminant/additive-free mepivacaine; and to determine the usefulness of a diagnostic protocol involving patch testing. METHODS: In a prospective study, 198 consecutive patients underwent collection of clinical data, skin prick tests and patch tests using allergens/antigens relevant for the investigation, and an intradermal/subcutaneous challenge procedure using contaminant/additive-free mepivacaine, as appropriate. Patients were followed up for 3 years for assessment of non-reactivity persistence using the same diagnostic protocol. RESULTS: Only one-third of the patients had a history of previous adverse local anaesthetic reactions. Absence of sensitization to contaminant/additive-free mepivacaine persisted in all subjects completing the follow-up. Controlled challenge with mepivacaine was negative in 196 patients with both negative specific skin prick tests and patch tests but it was eventful in two subjects with positive specific patch tests. A few subjects displayed positive skin prick tests and/or patch tests for latex and/or additives. CONCLUSIONS: A few patients had a relevant history for potential local anaesthetic-induced adverse reactions. Upon assessment of absence of sensitization and reactivity, contaminant/additive-free mepivacaine could safely be given for as long as 3 years. The patch testing was shown to be useful and safe for prediction of challenge outcomes. True allergic reactions to contaminant/additive-free mepivacaine were not observed in our patient series.     

An approach to the patient with a history of local anesthetic hypersensitivity: experience with 90 patients.

We have studied the utility of skin testing and progressive challenge to detect local anesthetic hypersensitivity in patients with histories of reactions to local anesthetics. The likelihood of previous immediate hypersensitivity reactions was determined by history in 90 referrals. Fourteen had histories compatible with immediate hypersensitivity reactions, 24 did not, and the history was uncertain in 52. Of the 14, 12 were negative to lidocaine skin test and challenge, although 5 gave histories of immediate hypersensitivity reactions to it. The other 76 patients also underwent skin testing and progressive challenge. No skin tests were positive with 1:100 local anesthetics but 10 patients had positive intradermal skin tests to undiluted 1% local anesthetics. Proof of false positivity was confirmed in 4 of 10 cases by uneventful challenge to the local anesthetic giving the positive skin test. At least 1 local anesthetic was cleared for use in each of the 90 patients. Skin testing as part of a progressive challenge protocol is a useful approach to the management of alleged local anesthetic hypersensitivity. True immediate hypersensitivity reactions to local anesthetics are rare. Positive skin tests to dilutions of 1:100 local anesthetics are also rare and may suggest the possibility of true immediate hypersensitivity to the agent tested.