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Background: Vancomycin infusion reaction (VIR), reportedly mediated through Mas-Related G Protein-Coupled Receptor-X2, is the primary vancomycin-induced immediate drug reaction. Clinically, distinguishing the underlying drug-induced immediate drug reaction mechanisms is crucial for future treatment strategies, including drug restriction, re-administration, and pretreatment considerations. However, the lack of validated diagnostic tests makes this challenging, often leading to unnecessary drug restriction., Objective: To determine whether intradermal tests (IDTs) and, separately, the basophil activation test (BAT) differentiate VIR from vancomycin-tolerant subjects., Methods: This was a cross-sectional study of vancomycin-exposed adults with and without a history of VIR. Data on demographics, allergy-related comorbidities, history of vancomycin exposures, and VIR characteristics were collected. IDT with vancomycin was performed. IDT dose-response EC 50 , IDT-related local symptoms, and BAT results were compared between groups., Results: A total of 11 VIR and 10 vancomycin-tolerant subjects were enrolled. The most reported VIR symptoms were pruritus (82%), flushing (82%), hives (46%), angioedema (27%), and dyspnea (19%). The IDT dose-response mean EC 50 was 328 μg/mL (95% CI, 296-367) in the VIR versus 1166 μg/mL (95% CI, 1029-1379) in the tolerant group (P < .0001). All VIR subjects reported IDT-related local pruritus compared with 60% of tolerant subjects (P = .0185). The %CD63 + basophils were consistently less than 2%, without significant differences between groups (P < .54)., Conclusions: Variations in skin test methodologies could help identify other immediate drug reaction mechanisms beyond IgE. This skin test protocol holds the potential for identifying VIR, particularly in cases where patients have received multiple drugs while BAT is insufficient. Future studies will validate and delineate its predictive value, assessing the risk of VIR., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

This article reviews our evolving understanding of penicillin hypersensitivity at the 80th anniversary of penicillin's clinical introduction. Penicillin breakdown products covalently bond to serum proteins, leading to classic drug hypersensitivity. Penicillin remains the most frequently reported drug "allergy." Adverse reactions were presumed, in retrospect incorrectly, to implicate a risk for anaphylaxis, and therefore skin testing for IgE became the focus. Skin test positivity may wane over time. This insight has led to the radical conclusion that penicillin hypersensitivity may not be "forever." Atopic background, other drug allergies, family history, gender, and race are apparently not risk factors for penicillin hypersensitivity. Confirmed penicillin hypersensitivity has declined since the 1960s, potentially due to "cleaner" penicillin products and lower dose oral, instead of parenteral, use. Avoiding penicillins, without evaluation, caused unanticipated problems that have been appreciated only recently including longer hospital stays, increased cost of care, suboptimal outcomes from serious infections, and greater toxicities and costs with alternative antibiotics. There are personal and public health advantages with broadly implemented penicillin allergy delabeling based on a reaction history-based risk assessment. Limited skin testing followed by an oral challenge, if negative, for higher-risk histories, and direct oral challenges in lower-risk individuals are currently the reference standard tests to confirm current tolerance., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Allergic reactions to the coronavirus disease 2019 (COVID-19) vaccines have raised concerns, particularly as repeated doses are required. Skin tests with the vaccines excipient were found to be of low value, whereas the utility of skin tests with the whole vaccine is yet to be determined., Objective: To evaluate a panel of skin tests and the outcomes of subsequent doses of immunization among subjects who suffered an immediate allergic reaction to the BioNTech (BNT162b2) COVID-19 vaccine., Methods: Between March and December 2021, patients who experienced symptoms consistent with immediate allergic reactions to the BNT162b2 vaccine and were referred to the Sheba Medical Center underwent skin testing with polyethylene glyol (PEG)-containing medicines, Pfizer-BNT162b2, and Oxford-AstraZeneca vaccine (AZD1222). Further immunization was performed accordingly and under medical observation., Results: A total of 51 patients underwent skin testing for suspected allergy to the COVID vaccines, of which 38 of 51 (74.5%) were nonreactive, 7 of 51(13.7%) had no skin sensitization but suffered a clinical reaction during skin testing (mainly cough), and 6 of 51 (11.7%) exhibited immediate skin sensitization. Both skin sensitization and cough during testing were related to a higher use of adrenaline following immunization (P = .08 and P = .024, respectively). Further immunization with the BNT162b2 vaccine was recommended unless sensitization or severe reaction to previous immunization was evident. The latter were referred to be tested/receive the alternative AZD1222 vaccine. Ten patients underwent skin testing with AZD1222: 2 of 10 (20%) demonstrated skin sensitization to both vaccines; thus, 8 of 10 were immunized with the AZD1222, of which 2 of 8 (25%) had allergic reactions., Conclusions: Immediate allergic reactions to COVID-19 vaccines are rare but can be severe and reoccur. Intradermal testing with the whole vaccine may discriminate sensitized subjects, detect cross-sensitization between vaccines, and enable estimation of patients at higher risk., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

In the western world, up to 10% of the general population and more than 15% of hospitalized patients report penicillin allergy. After a comprehensive evaluation, more than 95% of patients who report a penicillin allergy can subsequently tolerate this antibiotic. Traditionally, the most widely accepted protocol to evaluate beta-lactam (BL) allergy consisted of skin testing (ST) followed by a drug provocation test (DPT) in ST-negative patients. DPT is the gold standard for proving or excluding BL allergy and is considered the final and definitive step in the evaluation. Recently, studies have been published that support the use of direct DPTs without preceding ST for both pediatric and adult patients who report a low-risk historical reaction to BLs. However, these studies use various risk-stratification criteria to determine eligibility for a direct DPT. A standardized protocol for DPT is also lacking. In this review, we assess the current literature and evidence for performing direct DPT in the pediatric and adult populations. On the basis of this evidence, we also present risk-based algorithms for the evaluation of BL allergy in pediatric and adult populations based on a description of the historical reaction., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Cephalosporins, which belong to the beta-lactam therapeutic class, are increasingly used throughout the world. Few large studies on this issue have been conducted, and most of them have been performed as part of penicillin hypersensitivity studies., Objective: We described our 26-year experience exploring cephalosporin drug hypersensitivity, from which we identified epidemiological and cross-reactivity data., Methods: We included 476 patients who reported drug hypersensitivity reaction (DHR) to cephalosporin and underwent an allergy workup between January 1992 and July 2018 in the Allergy Unit of the University Hospital of Montpellier (France). According to their structural side chain R1 homology, we worked with 4 classes of cephalosporins. Logistic regression analysis was used to search for risk factors for hypersensitivity to cephalosporin (positive skin test [ST] or drug provocation test [DPT] results)., Results: Cephalosporin hypersensitivity was proven in 22.3% of the patients referred in our Unit, according to positive ST (51.9%) or DPT to the culprit drug (48.1%). One in 5 patients were children, and cephalosporin hypersensitivity was confirmed in 15% (47.6% of them by means of ST). In the cephalosporin hypersensitive population, initial reactions were mostly immediate (68.9%) and anaphylactic (72.7%). Cross-reactivity with aminopenicillins was the most frequent pattern of cross-reactivity. In multivariate analysis, immediate reactions (odds ratio [OR] = 3, 95% confidence interval [CI] [1.6-5.5], P < .001), anaphylactic shock (OR = 6.5, 95% CI [3.3-13.1], P < .001) and anaphylaxis (OR = 3.1, 95% CI [1.6-6.1], P < .001), and multiple reactions to the same or several cephalosporins (OR = 2.0, 95% CI [1-3.5], P = .04) were statistically associated with confirmed DHR. DPT was generally safe, but elicited anaphylaxis in 20% of patients. Systemic reactions during skin testing occurred in 9.1% of positive patients, almost always related to anaphylactic index reactions. Nonimmediate confirmed DHR to cephalosporins were rare and occurred in less than 10% of the positive patients., Conclusion: Almost a quarter of the tested patients were confirmed as hypersensitive to cephalosporins; sensitivity of skin testing was 51.9%, and thus, half of the positive patients needed a DPT to prove the diagnosis., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Penicillin and other beta-lactam antibiotics are recommended for group B Streptococcus and cesarean section prophylaxis, but approximately 10% of pregnant patients report a penicillin allergy., Objective: To assess the safety and impact of penicillin allergy evaluation in pregnant patients., Methods: In this retrospective study of obstetrician-ordered Allergy/Immunology (AI) electronic consultations (e-consults) from September 20, 2017 through December 31, 2019, we reviewed the electronic health record for e-consult recommendation; patient demographic, obstetric, and allergy histories; and peripartum antibiotic utilization with indication. For patients whose electronic consultation recommended an in-person AI evaluation, testing outcomes were determined, and multivariable logistic regression models were used to compare antibiotic use between patients who did and did not receive an in-person AI evaluation., Results: Of 389 obstetrician-ordered e-consults, 363 (93%) recommended an in-person AI evaluation; of these, 222 (61%) patients received an in-person AI evaluation. Of 220 (99%) patients skin tested, 209 (95%) had their penicillin allergy label safely removed. Compared with patients who did not receive an in-person AI evaluation despite it being recommended (n = 141), patients with in-person AI evaluation (n = 222) had reduced peripartum vancomycin (adjusted odds ratio [aOR], 0.07; 95% CI, 0.01-0.33), clindamycin (aOR, 0.17; 95% CI, 0.08-0.34), and gentamicin (aOR, 0.39; 95% CI, 0.19-0.78) use and increased penicillin (aOR, 18.0; 95% CI, 6.30-51.2) use. The fully AI evaluated patients had increased first-line antibiotic prophylaxis for group B Streptococcus (aOR, 26.9; 95% CI, 6.32-114) and cesarean section (aOR, 1.94; 95% CI, 1.06-3.52)., Conclusions: In a sample of 220 pregnant patients with penicillin allergy histories and in-person AI evaluation, penicillin allergy testing was safe and associated with significantly reduced broad-spectrum antibiotic use and increased first-line beta-lactam antibiotic use., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Drug allergy is frequently reported, but uncommonly confirmed with diagnostic testing. Although drug allergy assessments can improve clinical care, patient concerns may impact the optimal diagnostic approach and/or the clinical effectiveness of diagnostic testing., Objective: To assess drug allergy patient concerns., Methods: Using data from a multisite, prospective longitudinal cohort study, the United States Drug Allergy Registry (January 16, 2019, to January 24, 2020), we determined patient self-reported characteristics and qualitatively coded free-text patient concerns about their drug allergy/allergies. We assessed associations between patient characteristics and drug allergy concerns using multinomial logistic regression models., Results: Of 592 patients (mean age, 49 [standard deviation, 17] years, 74% female, 88% white), the most commonly reported drug allergies were penicillins (78%), cephalosporins (12%), and sulfonamides (12%) with common reactions of rash (62%), hives (54%), itching (48%), flushing or facial redness (28%), and swelling or angioedema (24%). Patient concerns, coded from free text, were optimal medication use (41%), no concern (17%), allergic reaction (14%), diagnosis (12%), and severe allergic reaction (12%). Using multinomial regression, the presence of drug allergy concerns increased with greater age, higher number of reported drug reactions, more antibiotic use, and certain reaction symptoms, most notably mouth or palate itching. Female sex was associated with increased severe allergic reaction concern. Poorer general and mental health was associated with increased allergic reaction concern., Conclusion: Patients with drug allergy were concerned about their options for medical treatment, having an allergic reaction, and receiving clarity about their diagnosis. Capturing and addressing patient concerns may improve the approach to patients with drug allergy and/or the effectiveness of drug allergy testing., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The involvement of small airways has recently gained greater recognition in asthma. Impulse oscillometry (IOS) is a simple and noninvasive method based on the forced oscillation technique, for the detection of small-airway dysfunction (SAD)., Objective: To identify the predictors of SAD in an unselected sample of 400 patients with physician-diagnosed asthma., Methods: All patients underwent standard spirometry and IOS at the first visit, and were stratified by the presence of SAD defined by IOS (fall in resistance from 5 to 20 Hz [R5-R20] > 0.07 kPa × s × L -1 ). Univariable and multivariable analyses and classification tree method were used to analyze cross-sectional relationships between clinical variables and outcome (SAD)., Results: SAD was present in 62% of the cohort. Subjects with SAD showed a less well-controlled asthma, according to the Global Initiative for Asthma definition, and a higher mean inhaled corticosteroid dosage use compared with subjects without SAD (both P < .001). Increased fractional exhaled nitric oxide (odds ratio [OR], 2.05; 95% CI, 1.14-3.70), female sex (OR, 2.27; 95% CI, 1.29-4.06), smoking (OR, 3.06; 95% CI, 1.60-6.05), older age (OR, 3.08; 95% CI, 1.77-5.49), asthma-related night awakenings (OR, 3.34; 95% CI, 1.85-6.17), overweight (OR, 3.64; 95% CI, 1.99-6.85), and exercise-induced asthma symptoms (OR, 6.39; 95% CI 3.65-11.45) were independent predictors of SAD. Classification tree analysis confirmed that exercise-induced asthma, overweight, asthma-related night awakenings, smoking, and older age have potential for clinical use in distinguishing patients with SAD from those without it., Conclusions: We identified predictors of SAD and showed that especially exercise-induced asthma, overweight, asthma-related night awakenings, smoking, and older age were strongly associated with SAD., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Recent single-center studies promote oral penicillin challenges, without skin testing, in patients with low risk/likelihood of true allergy. However, how best to define a low-risk penicillin allergy history is uncertain., Objective: To statistically determine an optimal low-risk definition, to select patients for safe outpatient penicillin challenges, without skin testing., Methods: In a multicenter Australian study (February 2016 to May 2018), testing strategy (skin test and/or oral penicillin challenge) and outcomes were retrospectively collected for all penicillin-allergic patients. Statistical modeling was performed with 8 low-risk definitions, to determine an optimal low-risk definition., Results: A total of 447 subjects (mean age, 45.3 years; 63.8% females) were analyzed. A history of benign, immediate, or delayed rash, more than 1 year before review, was the optimal low-risk definition. A total of 244 of 447 (54.6%) patients met this definition, of which 97.1% tolerated a 1- or 2-dose penicillin challenge, with no anaphylaxis in those who reacted. Of 203 patients designated higher risk, 54 (26.6%) had their allergy confirmed by skin test (n = 45) or challenge (n = 9)., Conclusions: History of penicillin-associated rash (without angioedema, mucosal ulceration, or systemic involvement), more than 1 year ago, is sufficient to select a patient for a direct oral penicillin challenge. This large multicenter study demonstrates that this approach appears safe, and risk is comparable to that in other procedures being performed in primary care in Australia. The higher risk patients are more likely to benefit from skin testing. This simple risk-based delabeling strategy could potentially be used by nonallergists, leading to more efficient penicillin allergy delabeling service provision., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Sulfonamide antimicrobials are commonly reported as causing drug allergy and have been implicated in a variety of hypersensitivity reactions including immediate IgE-mediated reactions, benign T-cell-mediated rashes, and severe cutaneous adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Cross-reactivity is unlikely between sulfonamide antimicrobials and sulfonamide non-antimicrobials. In patients who develop reactions to a sulfonamide non-antimicrobial, there is no evidence to suggest that sulfonamide antimicrobials and other sulfonamide non-antimicrobials would cross-react. Although immediate skin testing can be performed in patients with histories of immediate reactions, they are infrequently positive and wane over time. Delayed skin testing including patch tests to sulfonamides is rarely positive. Drug challenges are a useful tool for patients with both immediate and delayed reactions to sulfonamides. The role of sulfamethoxazole desensitization is controversial as rates of hypersensitivity reactions are similar between desensitization and drug challenge., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Cephalosporins are commonly used antibiotics both in hospitalized patients and in outpatients. Hypersensitivity reactions to cephalosporins are becoming increasingly common with a wide range of immunopathologic mechanisms. Cephalosporins are one of the leading causes for perioperative anaphylaxis and severe cutaneous adverse reactions. Patients allergic to cephalosporins tend to tolerate cephalosporins with disparate R1 side chains but may react to other beta-lactams with common R1 side chains. Skin testing for cephalosporins has not been well validated but appears to have a good negative predictive value for cephalosporins with disparate R1 side chains. In vitro tests including basophil activation tests have lower sensitivity when compared with skin testing. Rapid drug desensitization procedures are safe and effective and have been used successfully for immediate and some nonimmediate cephalosporin reactions. Many gaps in knowledge still exist regarding cephalosporin hypersensitivity., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The neuromuscular blocking agent (NMBA) rocuronium is a relevant cause of perioperative hypersensitivity (POH) with a significant risk of diagnostic error. Recently, it has been suggested to reclassify hypersensitivity to NMBA as type A reactions resulting from off-target occupation of the nonimmune MRGPRX2 receptor., Objective: To investigate whether basophil activation experiments can benefit diagnosis and add to the insights in the pathomechanisms of rocuronium hypersensitivity., Methods: A total of 140 patients with a suspected POH to rocuronium in whom peak tryptase was available had complete diagnostic workup for all potential culprits including triple confirmatory testing with skin tests, basophil activation test (BAT), and quantification of specific IgE (sIgE) antibodies to rocuronium and morphine. To further analyze the clinical relevance of sIgE antibodies, quantitative basophil inhibition experiments were performed by coincubation of the cells with rocuronium and morphine, an opiate known to harbor a substituted ammonium structure., Results: Diagnosis of rocuronium hypersensitivity was established in 72 of 140 patients (51.4%), of whom 65 (90.3%) demonstrated mast cell activation. Of the 72 patients, 64 displayed a positive skin test, 8 (11.1%) had their diagnosis documented only by BAT. Coincubation of morphine and rocuronium induced a dose-dependent inhibition of BAT with rocuronium that was restricted to 4 of 6 patients with IgE reactivity to rocuronium and/or morphine., Conclusions: BAT can benefit diagnosis of rocuronium hypersensitivity. As basophils barely express MRGPRX2 and BAT rocuronium can be inhibited by morphine, we believe that hypersensitivity to rocuronium still mainly results from IgE/high-affinity receptor for sIgE (FcεRI)-dependent effector cell activation. However, it cannot be excluded that in a few patients rocuronium hypersensitivity results from off-target occupation of the MRGPRX2 receptor., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Large-scale studies of drug provocation testing (DPT) or rapid drug desensitization (RDD) for hypersensitivity to antineoplastics and biologicals are scarce and limited to a few institutions., Objective: Our aim was to review our experience with DPT and RDD in a large number of patients with a history of hypersensitivity to antineoplastics and biologicals and summarize the practical implications of that experience., Methods: This was a 7-year prospective, observational, longitudinal study with reactive patients referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were selected after following our systematic and validated diagnostic approach (clinical history, skin test, risk assessment, specific IgE, DPT) before RDD. Candidate patients underwent RDD using the RCUH protocol. Cetuximab reactors underwent 1-bag RDDs., Results: A total of 1027 intravenous RDDs were performed using the RCUH protocol (399 platins, 395 taxanes, 178 biologicals, 55 other drugs), and 1026 were successfully accomplished in the 186 patients (of 515 referred patients) who met inclusion criteria for RDD. No breakthrough reactions occurred in 88% of RDDs. Most breakthrough reactions were mild. A total of 341 DPTs were performed, and 229 results were negative (67%). DPTs helped exclude hypersensitivity in 44% (229 of 515) of referred patients. In addition, 77 one-bag RDDs were performed in 6 cetuximab-reactive patients., Conclusions: This experience allows us to describe general management plans, as well as specific patient phenotypic patterns, predictors for reactions, and risk considerations that need a tailored approach (taking into account the 3 prominent drug categories: platins, taxanes, and biologicals)., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Drug allergy pathways are standardized approaches for patients reporting prior drug allergies with the aim of quality improvement and promotion of antibiotic stewardship. At the International Drug Allergy Symposium during the 2018 American Academy of Allergy, Asthma, and Immunology/World Allergy Organization Joint Congress in Orlando, Florida, drug allergy pathways were discussed from international perspectives with a focus on beta-lactam allergy pathways and pragmatic approaches for acute care hospitals. In this expert consensus document, we review current pathways, and detail important considerations in devising, implementing, and evaluating beta-lactam allergy pathways for hospitalized patients. We describe the key patient and institutional factors that must be considered in risk stratification, the central feature of pathway design. We detail shared obstacles to widespread beta-lactam allergy pathway implementation and identify potential solutions to address these challenges., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

All beta-lactam use is associated with a certain rate of adverse reactions. Many of these adverse reactions result in an allergy to the beta-lactam being entered into the patient's medical record. Unfortunately, only a small minority of these recorded allergies are clinically significant immunologically mediated drug hypersensitivity. An unconfirmed allergy to beta-lactams is a significant public health risk, because patients so labeled typically do not receive narrow-spectrum penicillins and cephalosporins when clinically indicated. The alternative antibiotics they receive result in poorer clinical outcomes, increased incidence of serious antibiotic-resistant infections, prolonged hospitalizations, and greater health care utilization. There is a wide variation in beta-lactam allergy incidence and prevalence around the world, based in part on the specific beta-lactams used and overused. There is a wide variation in specific protocols used to confirm current tolerance of beta-lactams and remove these inaccurate allergy reports. Harmonizing testing protocols, when possible, may lead to more widespread use of narrow-spectrum beta-lactams, when clinically indicated, and improve patient safety worldwide. Further research is needed to better understand the regional differences in reporting beta-lactam allergy as this relates to regional differences in beta-lactam use and overuse, the frequency of clinically significant immunologically mediated beta-lactam hypersensitivity, and the optimal testing strategies to confirm current tolerance, based on presenting clinical symptoms., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Epilepsy affects approximately 10 million children globally. Antiepileptic drugs (AEDs) are among the most frequent causes of drug hypersensitivity reactions (DHRs), especially severe ones. However, systematic studies about AED hypersensitivity among children are very rare. In this review, we aimed to gather all relevant and important data about different aspects of DHRs to AEDs in children by conducting a PubMed search including English-language studies published between January 1990 and June 2017. In these studies, aromatic AEDs were mostly incriminated in DHRs, but still being dominantly prescribed in both developed and developing countries. Although newer AEDs were increasingly prescribed owing to their presumed low toxicity profile, surveillance of DHRs is strongly recommended because case reports about severe reactions were recently reported. The pathogenesis seemed to be multifactorial including metabolic, genetic, and immunologic factors. Recent pharmacogenomic studies demonstrated strong genetic associations between some human leucocyte antigens and/or polymorphisms of AED metabolic enzymes and AED-induced DHRs among both adults and children. Young children, concurrent medications, a high starting dose and rapid dose escalation, and some genetic markers are important risk factors for AED-induced hypersensitivity. There were a very limited number of studies in the pediatric population evaluating the efficacy of different available diagnostic tools, such as intradermal, patch, and drug provocation tests. Data including mostly adult patients showed that patch tests had relatively high diagnostic value to identify the culprit with a positivity rate that ranged between 19.7% and 100% in delayed reactions to AEDs. Clinical cross-reactivity rates of 15% to 70% have been reported mainly between aromatic AEDs. In selected cases, where there is no other option, desensitization can be considered, although experience in children remained limited., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Proton pump inhibitors (PPIs) are commonly used to treat gastrointestinal diseases. Incidence of hypersensitivity reactions to PPIs has risen, likely because of increased consumption. Their diagnosis is difficult, with skin tests (STs) presenting low sensitivity, making it necessary to perform drug provocation tests (DPTs). The value of in vitro tests for the diagnosis of immediate reaction to PPI is unclear., Objective: To analyze the diagnostic value of the basophil activation test (BAT) in a group of patients diagnosed with immediate allergy to omeprazole., Methods: The study included 42 patients with confirmed immediate allergic reactions to omeprazole confirmed by positive ST results or DPT results and 22 age- and sex-matched subjects tolerant to PPIs. BAT was performed with omeprazole, pantoprazole, and lansoprazole using CD63 and CD203c as activation markers., Results: ST sensitivity was 66.7% with a specificity of 100%. BAT using CD63 with a stimulation index of more than 2 as positive revealed a sensitivity of 73.8%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 66.7%. BAT was positive in 57.1% of patients with negative ST result, and thus by combining ST and BAT we can correctly diagnose 85.7% of patients with immediate allergy to omeprazole., Conclusion: BAT represents a complementary tool for inclusion in the allergological workup for patients allergic to omeprazole. When combined with ST, it can be of value to guide the clinician as to whether to perform a DPT., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Unverified penicillin allergy leads to adverse downstream clinical and economic sequelae. Penicillin allergy evaluation can be used to identify true, IgE-mediated allergy., Objective: To estimate the cost of penicillin allergy evaluation using time-driven activity-based costing (TDABC)., Methods: We implemented TDABC throughout the care pathway for 30 outpatients presenting for penicillin allergy evaluation. The base-case evaluation included penicillin skin testing and a 1-step amoxicillin drug challenge, performed by an allergist. We varied assumptions about the provider type, clinical setting, procedure type, and personnel timing., Results: The base-case penicillin allergy evaluation costs $220 in 2016 US dollars: $98 for personnel, $119 for consumables, and $3 for space. In sensitivity analyses, lower cost estimates were achieved when only a drug challenge was performed (ie, no skin test, $84) and a nurse practitioner provider was used ($170). Adjusting for the probability of anaphylaxis did not result in a changed estimate ($220); although other analyses led to modest changes in the TDABC estimate ($214-$246), higher estimates were identified with changing to a low-demand practice setting ($268), a 50% increase in personnel times ($269), and including clinician documentation time ($288). In a least/most costly scenario analyses, the lowest TDABC estimate was $40 and the highest was $537., Conclusions: Using TDABC, penicillin allergy evaluation costs $220; even with varied assumptions adjusting for operational challenges, clinical setting, and expanded testing, penicillin allergy evaluation still costs only about $540. This modest investment may be offset for patients treated with costly alternative antibiotics that also may result in adverse consequences., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Perioperative anaphylaxis is an iatrogenic clinical condition, most often after anesthetic induction. Several mechanisms are implicated, including IgE- and non-IgE-mediated mechanisms. Perioperative anaphylaxis tends to be severe and has a higher mortality rate than anaphylaxis in other settings. This is partly due to factors that impair early recognition of anaphylaxis. Neuromuscular blocking agents, latex containing products, and antibiotics are the most common etiology. Chlorhexidine and dyes are increasingly culprits. The newest emerging cause is sugammadex, which is used for reversal of the effects of steroidal neuromusclar agents, such as rocuronium. Latex-induced allergy is becoming less common than in the 1980s due to primary and secondary prevention measures. Serum tryptase levels during the time of anaphylaxis and skin testing to suspected agents as an outpatient are necessary to confirm the diagnosis. Management includes epinephrine and aggressive fluid therapy. With radiocontrast media allergy, patients with a history of immediate hypersensitivity reactions to radiocontrast media should receive steroid and antihistamine premedication before re-exposure. Because IgE-mediated anaphylaxis to radiocontrast media is rare, there is a universal consensus that routinely skin testing all patients with a past reaction is not effective., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Hypersensitivity reactions (HSRs) to monoclonal antibodies (mAbs) are increasingly frequent as this class of therapeutic agents is rapidly expanding. Immediate and nonimmediate HSRs have been reported with mAbs. Immediate HSRs can be explained by 3 main mechanisms: cytokine release syndrome, IgE-mediated, and IgG-mediated reactions. Importantly, IgE-mediated reactions can occur on first exposure due to preformed specific IgEs, as shown for cetuximab. Almost all patients with an immediate HSR can be safely re-exposed either through desensitization or challenge depending on the severity and mechanism of the initial reaction. An algorithm detailing the general approach to these HSRs and the preferred method of re-exposure is presented in this review. Also, the mAbs that are most frequently implicated in HSRs are discussed individually., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Antibiotics are the most common class of medications that individuals report allergy or intolerance to. Adverse reactions are reported at a predictable rate with all antibiotic use that vary by antibiotic. Antibiotic allergy incidence rates are sex dependent, higher in females than in males. Most of these events are not reproducible or immunologically mediated. Antibiotic allergy prevalence increases with increasing age and is more common in hospitalized populations and in populations that use more antibiotics. Determining potential mechanisms for the observed symptoms of the adverse reactions is the starting point for effective management of antibiotic hypersensitivity. Skin testing and direct challenges are the primary tools used to determine acute tolerance in 2017. Commercially available in vitro testing is not currently clinically useful in determining antibiotic hypersensitivity, with rare exceptions. Desensitization can be used when acute-onset immunologically mediated hypersensitivity is confirmed to safely administer a needed antibiotic. Desensitization is not possible when clinically significant T-cell-mediated delayed-type hypersensitivity is present. Effective management of antibiotic allergy is an important part of a comprehensive antibiotic stewardship program., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Allergen skin prick testing remains an essential tool for diagnosing atopic disease and guiding treatment. Sensitivity needs to be defined for newly introduced devices., Objective: Our aim was to compare the performance of 10 current allergy skin prick test devices., Methods: Single- and multiheaded skin test devices (n = 10) were applied by a single operator in a prospective randomized manner. Histamine (1 and 6 mg/mL) and control diluent were introduced at 6 randomized locations onto the upper and lower arms of healthy subjects. Wheal and flare reactions were measured independently by 2 masked technicians., Results: Twenty-four subjects provided consent, and 768 skin tests were placed. Mean wheal diameter among devices differed from 3.0 mm (ComforTen; Hollister-Stier, Spokane, Wash) to 6.8 mm (UniTest PC; Lincoln Diagnostics, Decatur, Ill) using 1 mg/mL histamine (P < .001) and 4.8 mm (GREER Pick; Greer, Lenoir, NC) to 8.4 mm (Duotip-Test II; Lincoln Diagnostics, Decatur, Ill; and Sharp-Test; Panatrex, Placentia, Calif) using 6 mg/mL histamine (P < .001). The false-negative rates ranged from 0% to 45% with 1 mg/mL histamine. The analytical specificity was 100% for all devices tested. All devices were well tolerated, with average pain score of less than 4 on a 10-point visual analog scale. Pain scores were higher among women, but this did not reach statistical significance. The Multi-Test PC and the UniTest PC had the lowest pain scores compared with the other devices., Conclusions: All 10 skin prick test devices displayed good analytical sensitivity and specificity; however, 3 mm cannot arbitrarily be used as a positive threshold. The use of histamine at 1 mg/mL is unacceptable for certain devices but may be preferable for the most sensitive devices. On average, there was no pain score difference between multiheaded and single-head devices., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Oxaliplatin hypersensitivity (OXS) presents a challenge in the treatment of oxaliplatin-sensitive malignancies., Objective: To analyze patient characteristics of patients with OXS, skin test results, and desensitization outcomes to optimize management., Methods: Over 5 years, 48 patients with OXS were referred to the allergy/immunology unit at Massachusetts General Hospital. Their clinical reaction patterns were analyzed. Immediate hypersensitivity skin testing was used for risk stratification, and drug desensitizations were performed by using 3 related continuous intravenous protocols that were chosen based on clinical history, skin test reactivity, and the patients' previous desensitization outcomes., Results: OXS occurred in both sexes, with mostly gastrointestinal-related tumors. Hypersensitivity reaction (HSR) onset had occurred during any course of therapy (course nos. 1-28), with a median onset at course no. 8. HSR to oxaliplatin was similar to those observed with cisplatin and carboplatin, including cutaneous, cardiovascular, pulmonary, and gastrointestinal symptoms. However, neurologic symptoms, including tingling, and systemic symptoms, including fever and chills, occurred more often in patients with OXS. Unique to OXS, 2 patients developed drug-induced thrombocytopenia; 1 patients also developed drug-induced hemolytic anemia. Skin testing was positive for the majority of patients with OXS (27/46 [59%]) and correlated with a greater likelihood of developing an HSR during subsequent desensitizations. We safely performed 200 desensitizations in 48 patients with OXS., Conclusion: OXS is common with much similarity to other platin agents but also have distinct differences in the onset of hypersensitivity, sex, tumor type, drug-induced hemolytic anemia, and drug-induced thrombocytopenia. Skin testing was helpful for risk stratification. All of the desensitizations were completed successfully., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Penicillin skin testing is rarely used to undiagnose penicillin "allergy" in the United States, partially because of concern that commercially available materials are inadequate., Objective: We determined whether skin testing with only commercially available penicilloyl-poly-lysine and penicillin followed by an oral amoxicillin challenge, if skin test-negative, can safely identify clinically significant penicillin allergy., Methods: Five hundred sequential persons with positive history of penicillin "allergy" were evaluated by skin testing with penicilloyl-poly-lysine and penicillin between June 8, 2010, and March 29, 2012. All persons with negative skin tests were given an oral amoxicillin challenge and observed for 1 hour., Results: Persons undergoing penicillin allergy testing were representative of all health plan members with penicillin allergy. Only 4 persons (0.8%; 95% CI, 0.32%-2.03%) had a positive skin test result. Only 4 persons (0.8%; 95% CI, 0.32%-2.03%) had an acute objective oral amoxicillin challenge reaction. Fifteen persons (3.0%; 95% CI, 1.83%-4.98%) had subjective oral challenge reactions, either acute transient itching or dizziness. All were women and 11 (73.3%) had multiple drug intolerance syndrome. None had severe reactions or objective signs. These were not considered to be positive challenge reactions. Sixty-eight subjects (13.6%) who were negative on testing were exposed to 88 courses of penicillins during 90 days of follow-up. New reactions were reported after 4 courses (4.5%), 3 (75%) occurring in subjects with multiple drug intolerance syndrome., Conclusions: Penicillin skin testing, using only penicilloyl-poly-lysine and penicillin, followed by oral amoxicillin challenge, if negative, can safely identify clinically significant IgE-mediated penicillin allergy in patients who use health care in the United States at this time., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)