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Background: Antibiotics are the first-line treatment for bacterial infections; however, overuse and inappropriate prescribing have made antibiotics less effective with increased antimicrobial resistance. Unconfirmed reported antibiotic allergy labels create a significant barrier to optimal antimicrobial stewardship in health care, with clinical and economic implications., Objective: A systematic review was conducted to summarize the impact of patient-reported antibiotic allergy on clinical outcomes and various strategies that have been employed to effectively assess and remove these allergy labels, improving patient care., Methods: The review was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A critical appraisal was conducted on all studies and a narrative synthesis was performed to identify themes., Results: Four themes emerged: the prevalence of antibiotic allergy, impact of antibiotic allergy on antimicrobial prescribing, impact of antibiotic allergy on clinical outcomes, and delabeling strategies to improve clinical outcomes. Of the 32 studies, including 1,089,675 participants, the prevalence of reported antibiotic allergy was between 5% and 35%. Patients with a reported antibiotic allergy had poorer concordance with prescribing guidelines in 30% to 60% of cases, with a higher use of alternatives such as quinolone, tetracycline, macrolide, lincosamide, and carbapenem and lower use of beta-lactam antibiotics. Antibiotic allergy delabeling was identified as an intervention and recommendation to advance the state of the science., Conclusions: There is substantial evidence within the literature that antibiotic allergy labels significantly impact patient clinical outcomes and a consensus that systematic assessment of reported antibiotic allergies, commonly referred to as delabeling, improves the clinical management of patients., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Allergic reactions to antibiotics belong to hypersensitivity drug reactions and can trigger both immunoglobulin E-mediated symptoms and T cell-mediated symptoms. Skin manifestations are the most common symptoms. Although reporting a penicillin allergy results in considerable restrictions in the treatment of acute infections, which may be associated with poor treatment outcomes, in most cases the label 'penicillin allergy' is not called into question or critically reviewed. However, in 85-90% of patients, 'penicillin allergy' constitutes a mislabeling of a non-specific intolerance reaction that does not pose a risk to the patient when re-exposed to penicillins. Careful history taking, an evaluation of manifestations in the past, and easy-to-perform initial diagnostic steps are crucial in differentiating non-specific intolerance reactions from penicillin allergy sensu stricto. Thus, a penicillin de-labeling strategy allows for optimized antibiotic therapy in the event of a future infection. Although allergic cross-reactivity between different β‑lactam antibiotics can occur, the risk for a severe cross-reactivity is dependent on chemical properties of the specific β‑lactam. Published cross-reactivity tables can help in risk stratification and choice of alternative β‑lactam agents., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

An accurate diagnosis of IgE-mediated allergies is necessary to inform risk management for severe allergic reactions including anaphylaxis for food, venom, and drug allergies. The most widely available laboratory test for allergy is serum-specific IgE testing, which is routinely used for food allergy and insect sting allergy. Testing for specific IgE is limited by high sensitivity and low specificity, resulting in concern regarding overdiagnosis. Testing of allergen components has led to improved diagnosis for some food and venom allergens. Additional options for laboratory tests, such as epitope analysis, basophil activation, and mast cell activation, are being investigated for their potential to optimize diagnosis and provide predictors for reaction severity and treatment response. In contrast, laboratory testing for drug allergy is more limited because to date, there are no well-validated commercial assays in the United States. Furthermore, it is important to diagnose delayed reactions to medications, because these also significantly affect decision-making regarding therapeutic options for infectious disorders. Reliable tests for both immediate and delayed drug hypersensitivity are much needed, because drug allergy labels can significantly limit treatment options for patients. Research in this area is emerging., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: Penicillin allergy records are common, often incorrect and are associated with broad spectrum antibiotic use. We piloted a pharmacist-led multidisciplinary penicillin allergy de-labelling daily ward round to determine the opportunity for penicillin allergy de-labelling in a UK hospital., Methods: A daily ward round, delivered by antibiotic pharmacists or junior doctors, identified adult medical and surgical patients between 7 November 2022 and 31 January 2023 with a penicillin allergy record that was preventing first-line penicillin use. An allergy history was taken before risk stratifying likelihood of future harm from penicillin re-exposure and an allergy testing method was determined (direct de-label on history alone or after direct drug provocation testing). After successful allergy de-label, the antibiotic was switched to a penicillin antibiotic., Results: Of 7214 inpatients during the study period, 1133 (15.7%) had a penicillin allergy record. Of 285 allergy histories taken, 105 (36.8%) met high-risk criteria, 45 (15.8%) met low-risk criteria eligible for direct de-label and 73 (25.6%) met criteria eligible for direct drug provocation testing. We were unable to obtain a history for 61 (21.4%) patients. Of 45 low-risk patients eligible for direct de-label, 40 (88.9%) were de-labelled of whom 24 (53.3%) were switched to a penicillin antibiotic. Of 73 patients with a low-risk allergy history eligible for direct drug provocation testing, 16 (21.9%) received direct drug provocation testing, of whom 9 were switched to a penicillin antibiotic. Two direct de-label patients experienced harm (thrush within 5 days and delayed skin reaction after day 5); none of the direct drug provocation testing patients had a reaction by day 5. The switches resulted in reduced alternative antibiotic use by 173 Daily Defined Doses (DDDs)., Discussion: Penicillin allergy de-labelling patient pathway delivered by pharmacists and junior doctors was safe and effective and well accepted by patients and the wider clinical teams., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Summary: Background. Hypersensitivity reactions (HSR) to taxanes have been related to a complement activation by their excipients, polyoxyethylated castor oil and Polysorbate 80, structurally related to those of SARS-CoV-2 vaccines. The aim of this study was to verify the presence of a higher risk of HSR to SARS-CoV-2 vaccines in patients with history of HSR to taxanes. Methods. Patients with history of HSR to taxanes were evaluated before the vaccination in our center and underwent skin tests for PEG and Polysorbate 80 (PandP). Some patients completed the vaccination course in other centers without prior PandP skin tests because they had not manifested taxanes hypersensitivity before vaccination, or because those tests were not available. Results. 50 patients were evaluated. 100% of patients with history of hypersensitivity to taxanes completed the vaccine course with no cases of anaphylaxis. 33 underwent skin tests for PandP before the vaccination and no correlation was found between the positivity of PandP and taxanes skin tests (p = 0.538). 7 patients developed mild symptoms during skin tests and vaccination, similar but weaker than those suffered at the time of the taxane infusion, independently from the results of skin tests. Conclusions. In our cohort patients with history of reaction to taxanes were not at higher risk to develop anaphylaxis to SARS-CoV-2 vaccines. However, a common non-IgE mediated mechanism behind those HSRs cannot be completely excluded. This can only account for mild and harmless symptoms in case of SARS-CoV-2 vaccines. However, prudence is still recommended in these patients.

Background: Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting., Methods: We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines., Results: Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs., Conclusions: While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations.

Beta-lactam (BLM) antibiotics, including amino-penicillin and cephalosporins, are typically the first-choice treatment for bacterial infections. However, adverse reactions to these antibiotics are frequently reported, causing non-allergist physicians to select alternative broad-spectrum antibiotics that can have harmful consequences. Patients with unclear histories of hypersensitivity reactions to BLMs should undergo an allergy workup to establish a firm diagnosis, particularly when different drugs are prescribed simultaneously. However, finding the safest, most precise, and cost-effective methods for confirming BLMs hypersensitivity and selecting the most appropriate alternative BLM is uncertain, particularly in severe delayed reactions. This review aims to provide data and recommendations on the availability and validity of skin tests (STs), drug provocation test (DPT) protocols, based on the latest published literature and guideline. To make the process more practical, we focused on cross-reactivity between BLMs and diagnostic tests. There are two main novel aspects of this document: 1) For T-cell-mediated reactions, patient stratification into high, moderate, and low-risk groups based on the mortality and morbidity of adverse drug reactions. 2) For IgE-mediated reactions, stratification of individuals with isolated limited urticarial without anaphylaxis in a low-risk group and removal of the extensive limitation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Penicillin allergy is the most commonly reported drug allergy in the United States. Patients labeled with penicillin allergy are at risk of receiving broad-spectrum antibiotics for surgical site infection prophylaxis, which can lead to increased antibiotic resistance, higher morbidity, suboptimal antibiotic therapy, and higher medical costs. This study aimed to determine the true prevalence of penicillin allergy among surgical patients and to decrease the unnecessary use of broad-spectrum antibiotics., Methods: A retrospective chart review was performed of patients who underwent urogynecologic surgery in 2017. In 2018, a quality initiative was started, and all patients reporting penicillin allergies were offered antibiotic allergy testing as part of their preoperative testing., Results: In 2017, 15% of patients reported penicillin allergy and 52% of them received surgical prophylaxis with broad-spectrum antibiotics. In 2018, 463 patients underwent surgery, 55 of whom reported penicillin allergy and were offered penicillin allergy testing. 35 (64%) agreed to proceed with testing, and of those tested, 33 (94%) tested negative for penicillin allergy., Conclusions: 94% of patients with stated penicillin allergy who consented to allergy testing proved to have negative test. Penicillin allergy testing should be considered as part of preoperative management., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 National Association for Healthcare Quality.)

Background: Having a false penicillin-allergy label is linked to longer hospital stays and to an increased risk of Clostridioides difficile and meticillin-resistant Staphylococcus aureus infection., Aim: To assess a penicillin-allergy de-labelling tool designed for use by the non-allergist., Methods: Patients attending the surgical preoperative assessment clinic (POAC) at a large UK teaching hospital, who reported a penicillin allergy, were directly de-labelled by nursing or pharmacy staff, where appropriate. A penicillin-allergy de-labelling tool designed for use by the non-allergist was adapted and applied; nursing staff were provided with supporting information and education to enable removal of spurious labels. Antimicrobial pharmacists (AMPs) provided follow-up, cross-checked prophylactic antibiotics administered, interrogated clinical notes, and telephoned patients following their surgery, for details of any adverse reactions suffered., Findings: A total of 163 patients reporting a penicillin allergy were identified for intervention. Twenty-nine (17.8%) patients reported a penicillin-allergy history appropriate for direct de-labelling, of whom eight (27.6%) declined to consent. The remaining 21 patients (12.8%) were directly de-labelled, with 12 (7.4%) patients consenting during their POAC appointment; the remaining nine (5.5%) patients were consented and de-labelled after their surgery by an AMP., Conclusion: The POAC was identified as an appropriate location and time-point in the patient pathway to enable the direct removal of spurious penicillin-allergy labels prior to surgery. Results suggest that this could be undertaken by nursing staff, although support from AMPs enabled a greater number of patients to be de-labelled., (Copyright © 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Importance: Fewer than 5% of patients labeled with a penicillin allergy are truly allergic. The standard of care to remove the penicillin allergy label in adults is specialized testing involving prick and intradermal skin testing followed by an oral challenge with penicillin. Skin testing is resource intensive, limits practice to specialist-trained physicians, and restricts the global population who could undergo penicillin allergy delabeling., Objective: To determine whether a direct oral penicillin challenge is noninferior to the standard of care of penicillin skin testing followed by an oral challenge in patients with a low-risk penicillin allergy., Design, Setting, and Participants: This parallel, 2-arm, noninferiority, open-label, multicenter, international randomized clinical trial occurred in 6 specialized centers, 3 in North America (US and Canada) and 3 in Australia, from June 18, 2021, to December 2, 2022. Eligible adults had a PEN-FAST score lower than 3. PEN-FAST is a prospectively derived and internationally validated clinical decision rule that enables point-of-care risk assessment for adults reporting penicillin allergies., Interventions: Patients were randomly assigned to either direct oral challenge with penicillin (intervention arm) or a standard-of-care arm of penicillin skin testing followed by oral challenge with penicillin (control arm)., Main Outcome and Measure: The primary outcome was a physician-verified positive immune-mediated oral penicillin challenge within 1 hour postintervention in the intention-to-treat population. Noninferiority was achieved if a 1-sided 95% CI of the risk difference (RD) did not exceed 5 percentage points (pp)., Results: A total of 382 adults were randomized, with 377 patients (median [IQR] age, 51 [35-65] years; 247 [65.5%] female) included in the analysis: 187 in the intervention group and 190 in the control group. Most patients had a PEN-FAST score of 0 or 1. The primary outcome occurred in 1 patient (0.5%) in the intervention group and 1 patient (0.5%) in the control group, with an RD of 0.0084 pp (90% CI, -1.22 to 1.24 pp). The 1-sided 95% CI was below the noninferiority margin of 5 pp. In the 5 days following the oral penicillin challenge, 9 immune-mediated adverse events were recorded in the intervention group and 10 in the control group (RD, -0.45 pp; 95% CI, -4.87 to 3.96 pp). No serious adverse events occurred., Conclusions and Relevance: In this randomized clinical trial, direct oral penicillin challenge in patients with a low-risk penicillin allergy was noninferior compared with standard-of-care skin testing followed by oral challenge. In patients with a low-risk history, direct oral penicillin challenge is a safe procedure to facilitate the removal of a penicillin allergy label., Trial Registration: ClinicalTrials.gov Identifier: NCT04454229.

Background: Iodinated contrast media allergy is considered as a strong contra-indication for performing sialography. There is little evidence to support this approach., Objective: To evaluate the rate of iodinated contrast media (ICM) allergy in subjects undergoing sialography and to assess the risk for allergic responses in patients with a previous diagnosis of allergy., Methods: We retrospectively reviewed sialo-CBCT studies performed from 2014 to 2019. During the study period we implemented a protocol for performing sialo-CBCT in patients with a prior diagnosis of allergy: 1) Clinical data were collected from a questionnaire and medical records. 2) No premedication was administered but, instead, oxygen, epinephrine and a resuscitation cart were accessible. 3) Following the procedure, each patient was observed for one hour and contacted by telephone 24 hrs later., Results: No allergic responses were documented in the medical records of 1515 subjects following sialo-CBCT studies, including 13 individuals previously diagnosed with ICM allergy. Investigation of the subgroup with prior allergy disclosed that the range of injected volume was between 2 ml to 6.2 ml per patient and that complete secretion of ICM was detected in 7 of 13 patients. In the remainder of subjects, retention rates of 5-50% were observed., Conclusions: Allergic reactions are exceedingly rare following sialo-CBCT studies regardless of a previous diagnosis of allergy. Pre-medication with corticosteroids and antihistamines is usually not warranted.

Background: Nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity is common; however, many patients do not receive an accurate diagnosis and are using unnecessary alternative drugs or have medication restrictions., Objective: To establish a protocol for provocation tests that can be performed safely and effectively at home to give patients an accurate diagnosis, whereas also delabeling NSAID hypersensitivity., Methods: We retrospectively analyzed the medical records of 147 patients with NSAID hypersensitivity. All patients had NSAID-induced urticaria/angioedema with less than 10% body surface area skin involvement. One specialist developed the protocol through history taking and chart review. If NSAID hypersensitivity was confirmed, an oral provocation test was performed to confirm the safe alternative medications (group A). If it was undetermined, an oral provocation test was performed to confirm the diagnosis and alternative medications (group B). All oral provocation tests were performed by patients in their homes according to the protocol., Results: Approximately 26% of group A patients had urticaria or angioedema symptoms with alternative drugs, whereas the remaining 74% was safe. In group B, 34% of the patients were diagnosed with having NSAID hypersensitivity. However, 61% did not respond to the culprit drug; therefore, NSAID hypersensitivity had been misdiagnosed. During this at-home self-provocation test, no severe hypersensitivity reactions occurred., Conclusion: Many patients originally suspected of having NSAID hypersensitivity were confirmed to have been misdiagnosed. We successfully conducted an effective and safe at-home self-provocation test., (Copyright © 2023. Published by Elsevier Inc.)

The most common documented allergy is due to penicillin use, and penicillin allergy is often diagnosed early in childhood. However, fewer than 1% of the approximately 10% of the population with reported penicillin allergy have a true allergy. Antimicrobial stewardship programmes have employed pharmacist-led protocols to rechallenge patients with a documented history of penicillin allergy. There are published data to suggest that patients with a history of penicillin allergy can be successfully rechallenged and desensitised. We report a case of a 74-year-old woman with a documented childhood history of penicillin allergy who was rechallenged with amoxicillin/clavulanate (Augmentin) in the hospital during admission. She was given one trial dose of amoxicillin/clavulanate for the treatment of urinary tract infection to cover organisms detected in the urine culture. Amoxicillin/clavulanate was determined to be the most suitable antibiotic for empirical treatment. Given a documented history of penicillin allergy from over 60 years ago, the likelihood of reactivity was suspected to be low to none. The patient, however, developed an allergic reaction after the one-time oral amoxicillin/clavulanate 875/125 mg dose trial., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Immediate-type hypersensitivity reactions (IHRs) to carboplatin (CA) are most commonly reported in ovarian cancer patients. A 54-year-old woman with stage IV melanoma suffering from metastasis in the entire right lower extremity was presented to our allergy outpatient clinic for diagnostic work-up due to an anaphylactic reaction with palmoplantar erythema, conjunctivitis along with facial erythema, and an incipient decrease in blood pressure during a chemotherapy regimen with dacarbazine and carboplatin upon re-administration. A subsequently carried out allergological work-up with skin testing (ST) revealed CA to be the culprit drug, whereas cisplatin (CI) was confirmed to be a safe alternative for the patient for following treatments. Here, we report a case of an IHR to carboplatin in a melanoma patient, with CI serving as a safe alternative diagnosed by skin testing., (© 2022. The Author(s).)

Drug hypersensitivity reactions can be classified as immediate or delayed. While diagnostic options for immediate reactions are well developed and standardized, delayed reactions (in many cases type IV according to Gell and Coombs) are a challenge for allergy work-up. In recent years, some in vitro markers have been proposed and used for delayed reactions, such as contact dermatitis. Primary strategy: Avoidance is difficult to achieve, especially for COVID-19 vaccinations, when immunity against infection is extremely important. The aim of our study was to evaluate the application of in vitro delayed hypersensitivity tests in COVID-19 vaccines. Seven patients with a positive history of severe delayed drug allergy were enrolled. Vein blood was collected to stimulate cells with the tested vaccines (Comirnaty, Janssen, Spikevax) and excipients with the assessment of CD40L, CD69, IL-2, IL-4, IL-6, IL-10, IFNgamma, TNFalfa, and intracellular markers: granulysin and INFgamma. In addition, basophile activation tests, patch tests, skin prick tests, and intradermal tests were performed with the tested vaccine. Finally, the decision was made to either administer a vaccine or resign. Two out of seven patients were considered positive for drug hypersensitivity in the in vitro test according to the high vaccine stimulation index measured with CD69 (6.91 and 12.18) and CD40L (5.38 and 15.91). All patch tests, BATs, and skin tests were negative. Serum interleukin measurements were inconclusive as the impact of the vaccine itself on the immunity system was high. Intracellular markers gave uncertain results due to the lack of stimulation on the positive control. CD69 and CD40L could be reliable in vitro markers for delayed hypersensitivity to COVID-19 vaccines. Patch tests, skin tests, BATs, and serum interleukins did not confirm their usefulness in our study.

The global prevalence of β-lactam allergy poses a major challenge in administering first-line antibiotics, such as penicillins, to a significant portion of the population. The lack of β-lactam IgE antibody pools with defined selectivity hampers the standardization and validation of in vitro assays for β-lactam allergy testing. To address this limitation, this study introduces a synthetic IgE specific to β-lactam antibiotics as a valuable tool for drug allergy research and diagnostic tests. Using phage display technology, we constructed a library of human single-chain antibody fragments (scFv) to target the primary determinant of amoxicillin, a widely used β-lactam antibiotic. Subsequently, we produced a complete human synthetic IgE molecule using the highly efficient baculovirus expression vector system. This synthetic IgE molecule served as a standard in an in vitro chemiluminescence immunoassay for β-lactam antibiotic allergy testing. Our results demonstrated a detection limit of 0.05 IU/mL (0.63 pM), excellent specificity (100%), and a four-fold higher clinical sensitivity (73%) compared to the in vitro reference assay when testing a cohort of 150 serum samples. These findings have significant implications for reliable interlaboratory comparison studies, accurate labeling of allergic patients, and combating the global public health threat of antimicrobial resistance. Furthermore, by serving as a valuable trueness control material, the synthetic IgE facilitates the standardization of diagnostic tests for β-lactam allergy and demonstrates the potential of utilizing this synthetic strategy as a promising approach for generating reference materials in drug allergy research and diagnostics.

Drug hypersensitivity reactions are a serious concern in clinical practice because they can be severe and result in lifelong sequelae. An accurate diagnosis and identification of the culprit drug is essential to prevent future reactions as well as for the identification of safe treatment alternatives. Nonetheless, the diagnosis can be challenging. In vivo and in vitro tests can be helpful, although none are conclusive; therefore, the tests are not usually performed in isolation but as part of a diagnostic algorithm. In addition, some in vitro tests are only available in research laboratories, and standardization has not been fully accomplished. Collaborating research is needed to improve drug hypersensitivity reaction diagnosis. In this review, we update the current available in vivo and in vitro tools with their pros and cons and propose an algorithm to integrate them into clinical practice.

Background: An unconfirmed history of antibiotic allergies may negatively influence prescribing patterns for preoperative antibiotic prophylaxis and increase rates of postoperative wound infections through unnecessary use of alternative antibiotics., Methods: After a literature search, we developed a questionnaire for the structured collection of antibiotic allergy history in the anesthesia consultation center and tested it over 2 years at a tertiary care hospital under everyday conditions as part of a quality assurance project. All data were evaluated completely anonymously in the context of standard care., Results: After refining the questionnaire, we analyzed 4866 recorded optimized questionnaires, of which 51 were incomplete. An antibiotic allergy was denied 4312 times and affirmed 503 times, which corresponds to 10% in our sample. The most frequent single substances or groups in the 503 respondents with a positive history of antibiotic allergy were penicillin in 271 (54%), amoxicillin in 65 (13%), an unknown single agent in 50 (10%) and multiple substances in 25 (5%). The reported event occurred more than 10 years ago in 192 (38%) of the respondents, less than 10 years ago in 116 (23%), and 195 (39%) could not provide information. The time from exposure to symptom onset was less than 1h in 96 (19%), between 1 and 24 h in 75 (15%), more than 24 h in 106 (21%), and the remainder could not provide information. Allergy-specific treatment was recalled by 75 (15%) respondents, 287 (57%) reported not having received specific treatment, and the remainder could not recall. A specific allergy test was reported by 55 (11%) respondents, 337 (67%) said no allergy test had been made, and the rest could not recall. A substance-specific allergy passport was issued in 80 (16%) respondents. According to expert assessment, symptoms compatible with an IgE-mediated reaction were present in 96 (19%) of the respondents. An IgE-mediated reaction was considered possible in 70 (14%) and could be excluded by history in 337 (67%) of respondents. Out of 503 respondents with a positive history 51 (10%) could not remember the allergic substance but 7 (14%) of the 51 reported symptoms compatible with severe anaphylaxis or anaphylactic shock and 6 of the 51(12%) reported symptoms possibly related to an IgE-mediated reaction., Discussion: Our survey revealed approximately 10% of respondents reporting an antibiotic allergy, which is in the upper range of data published in international literature and corresponds most closely to American data. Thus, the topic is also relevant to German anesthesia consultation centers, given the high rate of respondents who could have been "delabeled" based on the comprehensive assessment of their history. More expert allergy testing is needed in patients who report symptoms related or probably related to an IgE-mediated reaction. In our opinion, a special issue exists in those patients who did not remember the exact antibiotic but reported symptoms compatible with severe anaphylaxis putting them at high risk of unintended re-exposure., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

A proper allergy work-up, based on the gold standard drug provocation test (DPT), usually rules out suspected drug hypersensitivity in children. These tests are generally open, given their high efficiency compared with double-blind placebo-controlled DPTs. Although their negative predictive value is excellent, no studies have calculated their positive predictive value, highly dependent on the prevalence of the disease. Most studies have found a rate of <5%-10% of true beta-lactam hypersensitivity in children. Given this low prevalence (pre-test probability), a few false-positive results can significantly reduce the estimated positive predictive value. False positives may arise from the nocebo effect during the test, including nocebo by proxy, or from observer bias, which depends on professional expertise and organizational circumstances. Some studies have found a high rate of tolerance on a second DPT in children who failed the first, but these results may be affected by the interval between the two tests, of a year or more in most cases, reflecting a loss of hypersensitivity over time. Taking into account the low rate of positive DPTs, with commonly mild reactions, we suggest confirming nonsevere positive DPTs with a second provocation performed soon after the first, especially in the case of beta-lactam antibiotics, in order to improve the diagnostic accuracy, de-label more patients, and achieve a better estimation of true drug hypersensitivity prevalence. In case of mild immediate reactions, the potential benefits of a second DPT should be carefully weighed against the risk of anaphylaxis., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose of Review: Perioperative anaphylaxis (POA) is rare but is associated with significant morbidity and mortality. Patients are referred to the allergist to identify the mechanism of the reaction, the causative agent and make recommendations regarding subsequent anaesthesia. Despite a well conducted allergological evaluation, the causative agent is not found in 30-60% of these reactions, leaving patients without a well established diagnosis., Recent Findings: Several mechanisms can induce POA. In addition to the well known IgE-mediated reactions, IgG-mediated reaction, MRGPR-X2-related reaction or nonspecific histamine release may be involved. These situations are not easily assessed by the allergological workup., Summary: When the allergological workup is negative, the situation should be reassessed with the team present at the time of the reaction to confirm the reality of the hypersensitivity reaction and to search for a possible differential diagnosis. If POA is confirmed, the allergological evaluation should be repeated, ensuring proper execution according to current guidelines and including the search for hidden allergens. Specific IgE assays or basophil activation tests may be of interest. In case of negative results, a closely monitored drug challenge test, in coordination with the anaesthesia teams, may be useful to avoid the exclusion of any drug injected during the reaction., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Drug hypersensitivity reactions are a diverse group of reactions mediated by the immune system after exposure to a drug. The Gell and Coombs classification divides immunologic DHRs into 4 major pathophysiologic categories based on immunologic mechanism. Anaphylaxis is a Type I hypersensitivity reaction that requires immediate recognition and treatment. Severe cutaneous adverse reactions (SCARs) are a group of dermatologic diseases that result from a Type IV hypersensitivity process and include drug reaction with eosinophilia and systemic symptom (DRESS) syndrome, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). Other types of reactions are slow to develop and do not always require rapid treatment. Emergency physicians should have a good understanding of these various types of drug hypersensitivity reactions and how to approach the patient regarding evaluation and treatment., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose of Review: Serum tryptase, a mast cell marker, provides clues for the mechanism, severity, and management of drug hypersensitivity induced by immunoglobulin E dependent or independent mast cell activation., Recent Findings: The interpretation of serum tryptase levels has been challenged during the last 2 years by major advances in tryptase genetics and their rapid incorporation into clinical practice. On the contrary, new pathophysiological insight into nonmast cell-dependent immediate hypersensitivity has been gained., Summary: This review provides up-to-date information on the pathophysiology and recommended use and interpretation of tryptase in the context of drug hypersensitivity reactions as a function of their endotype., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The aim of this study was to review the practice of general practitioners (GPs) in regard to the diagnosis and management of drug hypersensitivity reactions (DHRs) to identify major challenges and to facilitate the development of decision support tools to GPs confronted with DHRs patients., Recent Findings: DHRs are still a challenge in the GPs clinical practice, which implies difficulties in clinical decisions and referral to allergy specialists., Summary: DHRs can range from mild to severe and even life-threatening. Drugs are the main cause of anaphylaxis deaths in most countries. Most DHRs are firstly seen by GPs, paediatricians or emergency doctors. However, our systematic review demonstrated difficulties in differentiating DHRs from other drug side effects. Most DHRs epidemiological data are from hospital and emergency departments, which may not reflect the real-life experience in primary care. GPs should be aware of the alert signs of DHRs: the involvement of other systems beyond the skin and/or atypical skin/ mucosal involvement, which mandated immediate referral to an emergency department. Data still stress difficulties in the recognition of DHRs clinical manifestations and highlight the need for decision aids to support their management by GPs. Structured clinical history and clinical examination are key diagnostic tools. Reasons for referring to allergy specialists based on the literature are to investigate cause, to undergo specific procedure, such as desensitization and to identify well tolerated, alternative drugs., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The negative consequences of having a penicillin allergy label are well established. Penicillin allergy de-labelling improves healthcare outcomes; however, less attention is paid to modifying risk factors leading to penicillin allergy development. In this propensity score-matched retrospective cohort study, we used a de-identified population-based database (TriNetX Research Network) and examined the 30-day risk of acquiring a penicillin allergy label in patients using proton pump inhibitors (PPIs). We demonstrated a higher risk of acquiring a penicillin allergy label among PPI users compared to controls., (© 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

In the first wave of COVID-19, up to 20% of patients had skin lesions with variable characteristics. There is no clear evidence of the involvement of the SARS-CoV-2 virus in all cases; some of these lesions may be secondary to drug hypersensitivity. To analyze the possible cause of the skin lesions, we performed a complete allergology study on 11 patients. One year after recovery from COVID-19, we performed a lymphocyte transformation test (LTT) and Th1/Th2 cytokine secretion assays for PBMCs. We included five nonallergic patients treated with the same drugs without lesions. Except for one patient who had an immediate reaction to azithromycin, all patients had a positive LTT result for at least one of the drugs tested (azithromycin, clavulanic acid, hydroxychloroquine, lopinavir, and ritonavir). None of the nonallergic patients had a positive LTT result. We found mixed Th1/Th2 cytokine secretion (IL-4, IL-5, IL-13, and IFN-γ) in patients with skin lesions corresponding to mixed drug hypersensitivity type IVa and IVb. In all cases, we identified a candidate drug as the culprit for skin lesions during SARS-CoV-2 infection, although only three patients had a positive drug challenge. Therefore, it would be reasonable to recommend avoiding the drug in question in all cases.

Aims: Antibiotic allergy labels are common and associated with adverse care. Most people with an antibiotic allergy label are found to be non-allergic on investigation. The aims of this study were to evaluate the burden and accuracy of antibiotic allergy labels at North Shore Hospital and to identify and assess beta-lactam specific allergies, and the potential impact of an inpatient antibiotic allergy service., Methods: An evaluation of documented inpatient adverse drug reaction (ADR) labels. Structured assessment of beta-lactam allergies was undertaken using the Austin Health tool., Results: Three hundred and seven patients were reviewed; 78 patients had an antibiotic allergy label, with 102 individual labels. Fifty-five of these 78 patients underwent structured assessment. Forty-four patients had a beta-lactam-specific antibiotic allergy label. Using the Austin Health tool, 9/44 (20%) of beta-lactam-specific allergy labels could have been removed following a history alone and a further 16/44 (36%) would have been appropriate for direct oral challenge. Antibiotic allergy label accuracy was 64% for beta-lactam antibiotics, and 69% for non-beta-lactams., Conclusions: The prevalence of antibiotic specific allergies in our centre was similar to New Zealand and Australian statistics.1,2 Our study showed that a significant proportion of inpatients with a beta-lactam-specific allergy could be de-labelled on history or with a single dose challenge., Competing Interests: Nil, (© PMA.)

Objectives: Prudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a multidisciplinary expert committee to provide evidence-based recommendations for bedside decision-making in antibiotic therapy in patients that report an antibiotic allergy., Methods: The guideline committee generated 12 key questions, most of which were population, intervention, comparison, and outcome questions relevant to both children and adults with suspected antibiotic allergies. For each question, a systematic literature search was performed and reviewed for the best available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence was graded from very low to high, and recommendations were formulated in structured discussions as strong or weak., Results: Sixty recommendations were provided for suspected allergy to β-lactam antibiotics (BLAs) and non-β-lactam antibiotics. Owing to the absence of randomized controlled trials in this field, the underlying evidence was predominantly graded as low or very low. Available data support that a detailed allergy history should always be performed and critically appraised. When cross-allergy between BLA groups is not to be expected due to the absence of molecular similarity of the side chains, the patient can be safely exposed to the alternative BLA. An exception to this rule is severe delayed-type reactions in which re-exposure to a BLA should only be considered after consultation with a multidisciplinary team., Conclusions: Accumulated scientific data now support a more liberal approach that better balances the benefits of treatment with first choice and usually smaller spectrum antibiotics with appropriate avoidance of antibiotics in case of a truly high risk of a (severe) allergic reaction. In The Netherlands, a formal guideline was developed that provides recommendations for the approach toward suspected allergy to BLA and frequently used non-β-lactam antibiotics, thereby strongly supporting antimicrobial stewardship., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Delayed drug hypersensitivity reactions (DDHRs) represent a major health problem. They are unpredictable and can cause life-long disability or even death. The pathophysiology of DDHRs is complicated, multifactorial, and not well understood mainly due to the lack of validated animal models or in vitro systems. The role of the immune system is well demonstrated but its exact pathophysiology still a matter of debate., Area Covered: This review summarizes the current understanding of DDHRs pathophysiology and abridges the available new evidence supporting each hypothesis. A comprehensive literature search for relevant publications was performed using PubMed, Google Scholar, and Medline databases with no date restrictions and focusing on the most recent 10 years., Expert Opinion: Although multiple milestones have been achieved in our understanding of DDHRs pathophysiology as a result of the development of useful experimental models, many questions are yet to be fully answered. A deeper understanding of the mechanistic basis of DDHRs would not only facilitate the development of robust and reliable diagnostic assays for diagnosis, but would also inform therapy by providing specific target(s) for immunomodulation and potentially permit pre-therapeutic risk assessment to pursue the common goal of safe and effective drug therapy.

Background: Gadopentetic acid is a common contrast agent for enhanced magnetic resonance imaging. Adverse reactions due to gadolinium-based contrast agents are rare and easily overlooked by medical staff. A patient developed a rash as the first symptom and quickly developed a severe allergic reaction after receiving gadopentetic acid., Patient Presentation: A 74-year-old female patient was admitted on January 11, 2022, for femur magnetic resonance imaging. At 12:05 pm, a routine intravenous rapid injection of gadopentetic acid (15 ml) was given. Two minutes after administration, the patient developed skin itching. No obvious rash was found, but a 10 mg intravenous injection of dexamethasone was given., Recount of Events: After 1 minute, skin pruritus had not improved significantly, saliva secretion had increased significantly, and a general discomfort appeared. At 12:10 pm, outside the scanning room, the patient suddenly became unconscious; 1 mg of EPINEPHrine was injected intramuscularly, and oxygen was given through a mask. Heart rate, blood pressure, and oxygen saturation steadily dropped. The patient was transferred to the intensive care unit. After EPINEPHrine, norepinephrine, terlipressin, and dexamethasone treatments, the vital signs eventually stabilized. The patient was judged to have had a grade III severe allergic reaction according to the first aid guidelines for severe allergic reactions in China. The patient was discharged from the hospital on the morning of January 14., Conclusion: This case stresses the importance of being equipped with the medicines, items, supplies, and equipment needed for emergency treatments in all departments where contrast agents are used. Patients with apparently mild adverse reactions to contrast agents should not be overlooked., (Copyright © 2023 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Background: Diagnosis of perioperative anaphylaxis is often challenging. This study describes the utility of a newly developed tool for identifying patients with a high possibility of anaphylaxis, and aimed to investigate the frequency of anaphylaxis with each drug during the perioperative period in Japan., Methods: This study included patients with anaphylaxis of Grade 2 or higher severity during general anaesthesia at 42 facilities across Japan in 2019 and 2020. We developed and adopted a unique objective evaluation tool yielding a composite score for diagnosing anaphylaxis, which includes the results of skin tests and basophil activation tests, and clinical scores for perioperative anaphylaxis. The number of cases using each drug and the total number of anaphylaxis cases were investigated to calculate the frequency of anaphylaxis., Results: General anaesthesia was performed in 218 936 cases, which included 55 patients with suspected perioperative anaphylaxis. The developed composite score diagnosed 43 of them with a high probability of anaphylaxis. The causative agent was identified in 32 cases. Plasma histamine levels showed high diagnostic accuracy for anaphylaxis. The top causative agents were rocuronium (10 cases in 210 852 patients, 0.005%), sugammadex (7 cases in 150 629 patients, 0.005%), and cefazolin (7 cases in 106 005 patients, 0.007%)., Conclusions: We developed a composite tool to diagnose anaphylaxis, and found that the combination of tryptase levels, skin testing, and basophil activation testing results and clinical score improved the certainty of anaphylaxis diagnosis. The incidence of perioperative anaphylaxis in our study was 1 in about 5000 general anaesthesia cases., Clinical Trial Registration: UMIN000035350., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Neuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis., Methods: ALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated., Results: Overall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3-7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7-13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (<3%) for identifying NMBA-related reactions., Conclusions: Patients exposed to pholcodine 12 months before NMBA exposure have a significantly higher risk of an NMBA-related anaphylaxis. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related anaphylaxis., Clinical Trial Registration: NCT02250729., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: More than 90% of pediatric patients labeled with a penicillin allergy can tolerate subsequent treatment courses without reaction. Graded-dose challenges (GDCs) are an important tool to clarify reported penicillin allergy., Objective: To increase the use of same-day amoxicillin GDCs among patients with a low-risk penicillin allergy history who presented for outpatient allergy office evaluation from 2% to 15% and sustain for 6 months., Methods: New patients evaluated in an academic pediatric allergy clinic with a documented penicillin allergy were included, regardless of reason for referral. The percentage of these patients who were administered a GDC to amoxicillin at the initial evaluation was assessed over time. Multiple interventions were implemented to increase same-day GDC: amoxicillin, previously only available from pharmacy, was made available in clinic, and penicillin-allergic patients were scheduled earlier in the clinic session., Results: The baseline rate of new patients with penicillin allergy who received a GDC increased from 2% to 18% after amoxicillin was stocked in the allergy clinic. GDCs further increased to 34% after penicillin-allergic patients were scheduled at a time conducive to challenge., Conclusions: Amoxicillin availability in the clinic setting increased the percentage of eligible patients who completed same-day GDCs. Scheduling adjustments further increased the ability to conduct GDCs. Proactive penicillin allergy delabeling efforts can be assisted through practical approaches in the outpatient setting., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)