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Background: The first-line method in the diagnosis of patients who describe an immediate reaction after penicillin intake is a skin test (ST) with penicillin reagents. Objectives: We aimed to determine the safety and diagnostic value of penicillin STs in the diagnosis of immediate reactions to penicillins in pediatric patients. Methods: The study included pediatric patients with suspected immediate reaction to penicillin who were subjected to STs by using a standard penicillin test kit as well as suspected penicillin and the drug provocation tests (DPT) with the suspected penicillin at our clinic. Results: A total of 191 patients (53.9% boys) with a median age of 6.83 years (interquartile range, 4.2-12 years) were included in the study. The time from drug intake to the onset of reaction was ≤1 hour in 138 patients (72.3%) and 1 to 6 hours in 53 patients (27.7%). Penicillin allergy (PA) was confirmed by diagnostic tests in 36 of the 191 patients (18.8%). In multivariate logistic regression analysis, the history of both urticaria and angioedema (odds ratio [OR] 27.683 [95% confidence interval {CI}, 3.143-243.837]; p = 0.003) and anaphylaxis (OR 56.246 [95% CI, 6.598-479.489]; p < 0.001) were the main predictors of a PA diagnosis. Although ST results were positive in 23 patients (63.8%), 13 patients (26.2%) had positive DPT results despite negative ST results. The negative predictive value (NPV) of STs was calculated 92.2% (155/168). None of our patients experienced immediate or delayed systemic and/or local reactions in relation to the STs. Conclusion: A history of urticaria with angioedema and anaphylaxis were the main predictors of true PA in children with suspected immediate reactions. STs with penicillin reagents are safe for use in children. Although STs have a high NPV, DPT is the gold standard for diagnosis. DPTs should be performed as the final step of the diagnostic evaluation of PA in patients with negative ST results.

Background: Use of penicillin skin testing (PST) to rule out penicillin (PCN) allergies is safe and effective in immunocompetent patients; however, data on immunocompromised patients are limited., Objective: We aimed to determine safety, efficacy, and clinical impact of PST in immunocompromised patients with cancer., Methods: A quality improvement process establishing a PST service was implemented at MD Anderson Cancer Center. Adult patients admitted to leukemia and genitourinary medical oncology (GUMO) services with history of possible type I reactions to PCN were eligible for testing., Results: Between April and October 2017, 218 patients with reported PCN allergies were screened; 100 met inclusion criteria and underwent PST (67 leukemia, 33 GUMO). The most common reported allergy was to PCN (64%), with 61% reporting cutaneous reactions and 79% reporting reactions more than 20 years ago. PST with oral challenge results were overwhelmingly negative (95%); only 4% tested positive, and 1 test result was indeterminate (negative histamine control). After negative PST and oral challenge results, 51% patients were transitioned to PCN-based antibiotics during the same hospitalization. During the follow-up period (median 177 days), 65 of 95 patients were readmitted (185 total readmissions), and 51 patients required antibiotic therapy, with 37 receiving a PCN-based antibiotic (accounting for 336 days of therapy). No patient who received PCN-based antibiotics experienced an immediate-type allergic reaction., Conclusions: Our findings support PST use in immunocompromised hosts. The widespread use of PST in patients with cancer will allow for optimal use of antimicrobial therapy and stewardship, which are vital in a population at increased risk for infections., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The evaluation of antibiotic immediate-type hypersensitivity is intricate because of nonstandardized skin testing and challenge method variability., Objective: To determine the safety outcomes and risk factors for antibiotic challenge reactions in patients reporting a history of antibiotic immediate-type hypersensitivity., Methods: A 5-year retrospective review of patients evaluated for immediate-type antibiotic allergy was conducted. Data analyzed included patient demographics, index reaction details, and outcomes of skin testing and challenges, classified as single-step or multistep., Results: Antibiotic hypersensitivity history was identified in 211 patients: 78% to penicillins, 10% to fluoroquinolones, 7.6% to cephalosporins, and 3.8% to carbapenems. In total, 179 patients completed the challenges (median age 67 years, range 50-76 years, 56% women), and compared with nonchallenged patients, they reported nonanaphylactic (P < .001) and remote index (P = .003) reactions. Sixteen patients (8.9%) experienced challenge reactions (5 of 28 for single-step challenge, 11 of 151 for multistep challenge), and 11 of these patients had negative skin testing results before the challenge. Challenge-reactive patients were significantly younger (P = .007), more often women (P = .036), and had additional reported antibiotic allergies (P = .005). No correlation was detected between the reported index and observed challenge reaction severities (κ = -0.05, 95% confidence interval -0.34 to 0.24). Anaphylactic rates were similar during single-step and multistep challenges (3.6% vs 3.3%)., Conclusion: In the present population, younger women with multiple reported antibiotic allergies were at greatest risk for challenge reactions. Negative skin testing results did not exclude reactions, and index severity was not predictive of challenge outcome. The multistep and full-dose methods demonstrated a comparable reaction risk for anaphylaxis., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Skin tests for neuromuscular blocking agents (NMBAs) are not currently recommended for the general population undergoing general anaesthesia. In a previous study we have reported a high incidence of positive allergy tests for NMBAs in patients with a positive history of non-anaesthetic drug allergy, a larger prospective study being needed to confirm those preliminary results. The objective of this study was to compare the skin tests results for patients with a positive history of antibiotic-induced immediate type hypersensitivity reactions to those of controls without drug allergies., Methods: Ninety eight patients with previous antibiotic hypersensitivity and 72 controls were prospectively included. Skin tests were performed for atracurium, pancuronium, rocuronium, and suxamethonium., Results: We found 65 positive skin tests from the 392 tests performed in patients with a positive history of antibiotic hypersensitivity (1 6.58%) and 23 positive skin tests from the 288 performed in controls (7.98%), the two incidences showing significant statistical difference (p = 0.0011). The relative risk for having a positive skin test for NMBAs for patients versus controls was 1.77 (1.15-2.76). For atracurium, skin tests were more often positive in patients with a positive history of antibiotic hypersensitivity versus controls (p = 0.02). For pancuronium, rocuronium and suxamethonium the statistical difference was not attained (p-values 0.08 for pancuronium, 0.23 for rocuronium, and 0.26 for suxamethonium)., Conclusions: Patients with a positive history of antibiotic hypersensitivity seem to have a higher incidence of positive skin tests for NMBAs. They might represent a group at higher risk for developing intraoperative anaphylaxis compared to the general population., (Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Adverse reactions to local anesthetics (LA) are commonly reported in patients undergoing dental procedures and other minor surgical procedures. Most of these reactions, however, originate from psychosomatic, vasovagal or toxic conditions and are not immune-mediated. True immune-mediated reactions are considered extremely rare and are estimated to account for less than 1% of all adverse reactions to LA. On the other hand, almost all of the immune-mediated LA reactions that have been reported are related to adult patients. Here, however, we will present a pediatric case proven to be hypersensitive to two different amide-derivative LA's.

Background: Immediate hypersensitivity to corticosteroids is reported to occur with an incidence of 0.1%. The largest previous case series reporting corticosteroid skin testing has seven patients., Methods and Patients: We identified 23 patients (mean age 50 years, 65% female) from Auckland City Hospital who underwent skin testing (ST) for suspected corticosteroid hypersensitivity between July 2005 and April 2012. We performed a retrospective clinical case note review detailing clinical history of reaction, skin test results and subsequent management. Most patients (21/23) had a standard panel of testing with prednisolone, triamcinolone, methylprednisolone, hydrocortisone and dexamethasone. Skin tests used a 10% steroid stock concentration for skin prick tests (SPT) and dilutions of 1 : 1000, 1 : 100 and 1 : 10 for subsequent intradermal testing. A weal 3 mm greater than the negative control was considered positive., Results: A total of 23 patients were identified who had skin testing for suspected acute hypersensitivity to corticosteroids, eight of which had a history of anaphylaxis. From 28 reactions (in 23 patients), the most common route of administration was intra-articular (13), followed by oral (7), intravenous (3) and other (5). Skin tests were positive in 8/23 patients, and 7/8 of these patients had a history of corticosteroid-associated anaphylaxis. Skin tests were positive at either the skin prick test or intradermal stages. There was evidence suggesting clinical and skin test cross-reactivity between corticosteroids in one patient. One patient had a positive skin test, but negative oral challenge suggesting the skin test was false positive. Skin tests were negative in 15/23 patients. One patient had a negative prednisolone skin test and positive unblinded oral challenge, suggesting a false-negative skin test., Conclusions: Skin testing can provide sufficient evidence to diagnose allergy in patients with a clear history of immediate hypersensitivity to corticosteroids such as anaphylaxis. Both skin prick and intradermal tests should be used. There is evidence of cross-reactivity between steroids, so a panel is recommended. False-positive and false-negative reactions do occur; however, the frequency is unknown. Challenge remains the only definitive way to demonstrate a safe alternative to use., Clinical Relevance: As the largest case series described, this article provides new evidence for the interpretation of skin tests when investigating possible immediate hypersensitivity to corticosteroids., (© 2014 John Wiley & Sons Ltd.)

There are studies demonstrating that skin-test sensitivity to penicillins can decrease over time and that allergic patients may lose sensitivity if the responsible compounds are avoided. With regard to subjects with IgE-mediated hypersensitivity to cephalosporins, however, such studies are lacking. We evaluated prospectively in a 5-year follow-up 72 cephalosporin-allergic patients. After the first evaluation, patients were classified into two groups according to their patterns of allergologic-test positivity: to both penicillins and cephalosporins (group A), or only to cephalosporins (group B). Skin tests and serum-specific IgE assays were repeated 1 year later and, in case of persistent positivity, 3 and 5 years after the first allergologic examination. Seven (43.7%) of the 16 subjects of group A and 38 (67.8%) of the 56 patients of group B became negative; one was lost to follow-up. Patients of group B became negative sooner and more frequently than group A subjects., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hypersensitivity reactions to β-lactam and non-β-lactam antibiotics are commonly reported. They can be classified as immediate or nonimmediate according to the time interval between the last drug administration and their onset. Immediate reactions occur within 1 hour after the last drug administration and are manifested clinically by urticaria and/or angioedema, rhinitis, bronchospasm, and anaphylactic shock; they may be mediated by specific IgE-antibodies. Nonimmediate reactions occur more than 1 hour after the last drug administration. The most common manifestations are maculopapular exanthems; specific T lymphocytes may be involved in this type of manifestation. The diagnostic evaluation of hypersensitivity reactions to antibiotics is usually complex. The patient's history is fundamental; the allergic examination is based mainly on in vivo tests selected on the basis of the clinical features and the type of reaction, immediate or nonimmediate. Immediate reactions can be assessed by immediate-reading skin tests and, in selected cases, drug provocation tests. Nonimmediate reactions can be assessed by delayed-reading skin tests, patch tests, and drug provocation tests. However, skin tests have been well validated mainly for β-lactams but less for other classes of antibiotics., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Immediate hypersensitivity reactions (IHR) to iodinated contrast media (ICM) have traditionally been considered nonallergic; however, the increasingly frequent reporting of positive skin test and basophil activation test results suggests a specific allergic mechanism in some patients. Skin tests have been proposed as a useful tool for diagnosis, although their sensitivity and predictive values remain to be determined. The role of controlled challenge testing has not been assessed., Objective: We aimed to evaluate the role of controlled challenge testing in skin test-positive IHR to ICM., Patients and Methods: We evaluated 106 patients with IHR to ICM by performing skin tests with the agent that caused the reaction. Patients with a positive result were selected. Skin tests were extended to a series of 8 ICMs; 5 patients underwent controlled challenge test with an alternative skin test-negative ICM; a further 2 patients underwent computed tomography with an alternative skin test-negative ICM. No premedication was administered., Results: Intradermal test results were positive to the ICM that caused the reaction in 11 out of 106 patients (10.4%). Five of the 11 patients tolerated a controlled challenge test with an alternative skin test-negative ICM. The 2 patients who underwent computed tomography with an alternative skin test-negative ICM tolerated the medium., Conclusions: Skin tests are useful for the diagnostic workup in patients with an allergic IHR to ICM. Since ICM cannot be avoided in many patients because they are irreplaceable in some diagnostic or therapeutic techniques, an alternative safe ICM should be investigated for future procedures. We propose the use of controlled challenge tests based on skin test results to address this need in skin test-positive reactions in order to identify an alternative non-cross-reactive ICM.

Allergy to neuromuscular blocking agents (NMBAs) is the most important caue of perioperative anaphylaxis in France. The diagnosis relies on a careful clinical history, the search of serum IgE antibodies, and the realization of skin tests. Although the skin tests are the most important tool and their sensitivity is widely recognized, the lack of information about their negative predictive value represents an important issue in the management of patients who require a new procedure with NMBA injection. We present a series of 49 patients with confirmed allergy to NMBAs, six of whom required a subsequent surgery with neuromuscular blockade. Negative skin tests allowed the selection of an alternative NMBA, which was well tolerated in all 6 cases. We found an excellent negative predictive value of skin tests in our series but larger studies are required to properly address this question., (© 2011 John Wiley & Sons A/S.)

Background: Allergy to penicillins remains an important issue. Penicillin skin testing (PST) with major and minor determinants has been shown to be a highly valuable tool for identifying IgE-mediated penicillin allergy. The value of additional testing with side-chain-specific moieties from semisynthetic penicillins such as amoxicillin is not well-established in spite of the widespread use of these medications., Methods: A retrospective review of all consecutive inpatient PST results from 1995 to 2007 comprising 1,068 patients was performed in our institution on individuals with a self-reported history of beta-lactam allergy to assess the importance of including the amoxicillin determinant in a previously validated PST panel. Descriptive statistics were performed. The PST panel included penicilloyl-polylysine, penicillin G, penicilloate, penilloate and amoxicillin., Results: Of 1,068 patients, 243 (23%) had a positive skin test reaction on the PST panel. Testing with amoxicillin was positive in 30.9% of patients, the majority of whom (81%) were also positive to 1 or more standard penicillin reagents. Fourteen of the 243 positive patients (5.8%) had a positive skin test reaction only to amoxicillin. Additionally, the use of penicilloate and penilloate minor determinants in combination with penicillin G identified a greater percentage of penicillin-allergic individuals compared to using only penicillin G (22.6 vs. 6.6%), demonstrating their importance in the PST panel., Conclusions: These data indicate that the inclusion of the amoxicillin determinant appears to identify a small but important group of allergic individuals who may otherwise test negative on a PST panel., (Copyright 2010 S. Karger AG, Basel.)

Skin tests with drugs help determine the cause and mechanism of drug hypersensitivity reactions. The diagnosis of adverse drug reactions is based primarily on history and clinical presentation. In type I, IgE-mediated allergic drug reactions, skin prick test and intradermal testing may provide rapid and supportive evidence for diagnosis or exclusion of IgE-mediated reactions. These tests often are more sensitive than laboratory assays for IgE antibodies to drug allergens, which are available only for a few drugs. Because intradermal skin tests occasionally induce adverse events, they should be performed by experienced personnel in an adequate environment.

Purpose of Review: The present review addresses the most recent literature regarding the diagnosis of drug hypersensitivity reactions, which can be classified as immediate or nonimmediate according to the time interval between the last drug administration and the onset. Immediate reactions occur within 1 h; nonimmediate ones occur after more than 1 h., Recent Findings: Clinical and immunological studies suggest that type-I (IgE-mediated) and type-IV (cell-mediated) pathogenic mechanisms are involved in most immediate and nonimmediate reactions, respectively. New diagnostic tools, such as the basophil activation test and the lymphocyte activation test, have been developed and are under validation., Summary: In diagnosis, the patient's history is fundamental; the allergologic examination includes in-vivo and in-vitro tests selected on the basis of the clinical features. Prick, patch, and intradermal tests are the most readily available forms of allergy testing. Determination of specific IgE levels is still the most common in-vitro method for diagnosing immediate reactions. The sensitivity of allergologic tests is not 100%; in selected cases, therefore, provocation tests are necessary. The routine use of the basophil activation test and the lymphocyte activation test could increase the sensitivity of diagnostic work-ups, thus reducing the need for drug provocation tests.

Background and Objectives: To analyse the prevalence of positive prick-tests to all medicaments normally checked in allergy units when a patient is suspected of being allergic to anaesthetics. To establish the degree of agreement between the antecedents of a previous history of an allergic reaction to a medicament and the positive result, or not, to the specific prick-test for the said medicament., Methods: This was a prospective study, during 2003 and 2004, which analysed 473 patients referred by their doctors to allergy units to make retrospective diagnoses of an allergy to a drug. The prick-test was done using the undiluted drug. All patients were tested for 41 drugs. These include antibiotics, trimethoprim-sulphamethoxazole, non-steroidal anti-inflammatory drugs (NSAIDs) and perioperative drugs (PD): neuromuscular blocking drugs, latex, iodine, local anaesthetics, hypnotics, opioids and coadjuvants. Cohen's Kappa Index was used to determine the degree of agreement., Results: 71.5% of patients studied presented a positive prick-test. The largest number of positive cases was found in antibiotics (56.4%), followed by PD (15.6%), NSAIDs (14.4%) and trimethoprim-sulphamethoxazole (12.7%). Among PD, the highest prevalence of positive prick-tests was found for neuromuscular blocking drugs (5.3%). Agreement between the substance suspected of causing the allergic reaction and the positive prick-test was excellent for penicillin (Kappa = 0.74) and other antibiotics (Kappa = 0.721) and good for NSAIDs (Kappa = 0.47) and iodine (Kappa = 0.54)., Conclusions: The prevalence of patients with positive prick-tests to PD occurred in 15.6% in this prospective cohort. Neuromuscular blocking drugs were found to have the highest prevalence of positive prick-tests. There is positive agreement when the substance responsible for the allergic reaction is suspected, otherwise agreement is low.

Objective: The aim of this study was to assess the reliability of a diagnostic protocol, the incremental challenge test (ICT), for patients with and without a history of adverse reactions to local anesthetics (LAs) or other drugs, to select an LA that could be safely used., Study Design: The ICT was performed on 432 subjects, 314 female and 118 male. Four hundred thirty-two challenges were carried out with LAs that were free of adrenaline and preservatives. Chi-square analysis was performed to evaluate the existence of different predispositions to ICT positivity among subjects of the 4 categories studied., Results: Four hundred fifteen tests were completed with no clinical events occurring. The analysis did not show any significant difference (chi-square = 6.17; P >.05)., Conclusions: Our results confirm that immunoglobulin E-mediated reactions to LAs are uncommon and that the ICT offers safety and specificity in diagnosing adverse reactions to LAs, allowing for the selection of a safe and reliable LA.