Search

Rationale: Although rare, systemic hypersensitivity reactions to nedaplatin chemotherapy arise rapidly and can be life-threatening. The causes are unclear, and multiple potential mechanisms exist. Here, we report a case of systemic hypersensitivity reaction to nedaplatin and review the literature to establish a recommended protocol., Patient Concerns: A 62-year-old man was being treated for squamous lung cancer with multiple metastases. On the first day of chemotherapy, 5 minutes after nedaplatin infusion, he developed panic, shortness of breath, and dyspnea with rapid heart rate, reduced oxygen saturation, and elevated blood pressure., Diagnoses: The symptoms indicated that the patient had developed a severe hypersensitivity reaction to nedaplatin, which could be life-threatening without immediate intervention., Intervention: Nedaplatin was discontinued, and he was treated with oxygen, ECG monitoring, finger pulse oximeter monitoring, 10 mg dexamethasone sodium phosphate injected intravenously, 20 mg diphenhydramine hydrochloride injected intramuscularly, and 40 mg methylprednisolone sodium succinate injected intravenously., Outcome: His allergic symptoms resolved, and once his vital signs stabilized, he was given 5 mg oral desloratadine once daily and 10 mg oral ebastine once daily to alleviate the effects of the allergic reaction. Once his vital signs remained stable without any special supportive treatment, he was discharged from the hospital. His chemotherapy regimen was discontinued, with no plan for a follow-up treatment due to the possibility of cross-allergic reactions between platinum-based drugs., Lessons: Clinical use of nedaplatin should be monitored and managed intensively for prevention and treatment of hypersensitivity reactions. Care should be taken to control the titration rate during infusion while closely monitoring vital signs. Clinical staff should be prepared to treat allergic symptoms as soon as they appear. The acute phase should involve immediate discontinuation of the drug; intravenous saline infusion for volume expansion; rapid assessment of circulation, airway, respiration, state of consciousness, and skin condition; and administration of oxygen, antihistamines, and epinephrine as appropriate for anaphylaxis. More randomized clinical trials are needed to elucidate appropriate preventative and management strategies to improve patient safety and support their successful completion of clinical treatment programs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: Many systemic medications have been observed to cause ocular toxicity. A subset of these reactions is thought to involve immunomodulation or a hypersensitivity reaction. As new medications are developed, ocular adverse effects are becoming increasingly prevalent. Herein we review immune-mediated drug reactions affecting they eye with special attention to the hypersensitivity mechanisms leading to ocular toxicity., Recent Findings: Recent work has focused on mechanisms and risk of immune-mediated ocular adverse drug reactions including genetic susceptibility and loss of ocular immune privilege., Summary: Given the consequences of immune-mediated ocular adverse drug reactions, clinicians must be aware of these to facilitate early recognition and management. The prompt involvement of an ophthalmologist for diagnosis and management is often essential to preserve vision and avoid long-term morbidity., (Copyright © 2023 Wolters Kluwer Health, 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.)

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.)

Background: Chlorhexidine generally has a good safety profile. However, allergic reactions are reported with increasing frequency. In China, it is rarely reported, and its characteristics are unknown. The purpose of this study was to summarize the experience of a Chinese allergy center with chlorhexidine allergy., Methods: The authors retrospectively reviewed all patients who underwent chlorhexidine allergy testing in the Allergy Center of West China Hospital, Sichuan University (Chengdu, China), in the period February 2018 to May 2022 (n = 43 patients) and included the patients diagnosed with chlorhexidine allergy for analysis., Results: Ten patients who were diagnosed by skin prick and serum-specific immunoglobulin E tests were included. They experienced a total of 30 allergic reactions to chlorhexidine (mean ± SD, 3.0 ± 1.3). Five patients experienced six allergic reactions (6 of 30, 20%) during general or local anesthesia, and they may have been exposed to chlorhexidine via different routes. Only one allergic reaction (1 of 30, 3%) was recorded with exposure via a mouthwash. The other 23 allergic reactions (23 of 30, 77%) were caused via a skin disinfectant; the route of exposure was IV cannulation in 22 allergic reactions (22 of 23, 96%) and broken skin in one allergic reaction (1 of 23, 4%). The symptoms included a quick onset and great severity. Two patients (2 of 10, 20%) had been accidentally re-exposed to chlorhexidine after diagnosis., Conclusions: This study conducted in China showed that the majority of reactions to chlorhexidine were attributed to skin disinfectants, and IV cannulation was the most common exposure route; in general, however, chlorhexidine allergy was easily overlooked. The potential allergenicity of chlorhexidine used for skin preparation before IV cannulation or should be considered in patients who develop allergic reactions perioperatively., (Copyright © 2023, the American Society of Anesthesiologists. All Rights Reserved.)

Introduction: Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and mortality., Patient Concerns: A 52-year-old man was hospitalized for developing a rash after 3 weeks of sulfasalazine treatment for ulcerative colitis (UC)., Diagnosis: The patient was diagnosed with DHS based on his drug history, clinical manifestations, and laboratory test results., Interventions: The patient was administered intravenous glucocorticoids. The patient's condition improved after treatment with human immunoglobulin and antihistamines., Outcomes: Combination therapy of glucocorticoid and gamma globulin, the whole-body pruritus disappeared, and no new rash appeared. The whole-body rash subsided or turned dark red., Conclusion: This article describes the diagnosis and treatment process of a case of sulfasalazine-induced DHS and reviews the relevant literature to improve clinician understanding and avoid misdiagnosis and missed diagnosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: There is a broad spectrum of chemotherapy-induced adverse reactions. Hypersensitivity reactions are being extensively studied as they can affect the ideal treatment. The goal of this review is to describe the current management of adverse reactions to chemotherapy, focusing on hypersensitivity events., Recent Findings: The range of possible desensitization protocols is increasing, as well as the delabeling algorithms and diagnostic tools. One-bag desensitization protocols, omalizumab use in immediate hypersensitivity reactions, slow desensitization protocols in nonimmediate hypersensitivity reactions and standardization of skin tests for platinum drugs, are some examples., Summary: The handling of adverse reactions to chemotherapy is evolving, with the increasing identification of hypersensitivity reactions and the development of strategies for their management, to maintain the culprit drug., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Drug desensitization is the only therapeutic option for patients with drug allergies who need to receive the drugs they are allergic to, and it is especially critical in patients with an urgent need for chemotherapy, biologics, or antibiotics, where equally effective alternatives might not be available. However, drug desensitization is not a cookbook where anyone with no experience or specific training can find a general recipe. This review article will approach the singularities that make personalized and highly specialized care essential in this field., Recent Findings: Drug desensitization needs to be personalized for each individual patient bearing in mind countless factors. Recent articles have tried to define the optimal resources and the most important factors to account for in personalization. However, drug desensitization is only a tool within the wider management pathway, and we will discuss recent findings in allergy delabelling in chemotherapy, biologics, and antibiotics., Summary: Risk-assessment, delabelling, and desensitization protocols, as a part of wider management pathways, can be adapted locally along with comprehensive and multifactorial risk-management strategies. These high-complexity and high-risk procedures, such as drug desensitization, need to be managed by expert allergists who can provide personalization, innovation, continuous improvement, research, and teaching in expert centres., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

Purpose of Review: The goal of this article is to provide an updated understanding and evidence-based approach where possible for antifungal hypersensitivity. This includes recognition of clinical phenotype, implications for cross-reactivity and diagnostic, and management strategy for immediate and delayed hypersensitivity reactions., Recent Findings: Antifungal hypersensitivity reactions can be classified according to their latency (immediate or delayed) and clinical phenotype. The majority of the cases described in the literature are delayed T-cell mediated reactions of various severities but immediate reactions consistent with non-Immunoglobulin E (IgE)-mediated mast cell activation and IgE-mediated reactions have also been described. Ancillary information such as skin testing, drug challenge and ex vivo experimental approaches can aid causality assessments and inform antifungal class cross-reactivity, which help optimize antifungal prescribing and stewardship., Summary: This review will update the clinician on mechanisms of drug hypersensitivity as well as providing a structured approach to the recognition, diagnosis and management of antifungal hypersensitivity reaction., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The epidemiology of hospital adverse reactions (ARs), particularly allergic reactions, or hypersensitivity reactions (HSRs), is poorly defined. To determine priorities for allergy safety in healthcare, we identified and described safety reports of allergic reactions., Methods: We searched the safety report database of a large academic medical center from April 2006 to March 2016 using 101 complete, truncated, and/or misspelled key words related to allergic symptoms, treatments, and culprits (e.g., medications, foods). Patient and event data were summarized for ARs and two types of ARs, HSRs and side effects/toxicities., Results: Among 9111 key word search-identified events, 876 (10%) were ARs, of which 436 (5%) were HSRs and the remaining 440 (5%) were side effect reactions or toxicities. Whereas the most common HSRs were simple cutaneous reactions (83%), the following severe immediate HSRs were also identified: shortness of breath (16%), anaphylaxis (14%), and angioedema (12%). Most HSRs were caused by drugs (81%), with antibiotics (26%), particularly β-lactams (11%), and vancomycin (8%), commonly implicated. Other causes of drug HSRs included contrast agents (24%), chemotherapeutics (7%), and opioids (6%). Nondrug HSRs were from blood products (8%), latex (3%), and devices (3%). Food reactions were rarely identified (1%)., Conclusions: We identified ARs, HSRs, and side effects/toxicities, contained in a decade of safety reports at an academic medical center. Allergy safety in the healthcare setting should target approaches to common and severe reactions, with a focus on the safe administration of β-lactams, vancomycin, contrast agents, chemotherapeutics, and opioids. Priority nondrug HSR culprits include blood products, latex, and devices., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Children with mitochondrial disease undergo anesthesia for a wide array of surgical procedures. However, multiple medications used for their perioperative care can affect mitochondrial function. Defects in function of the mitochondrial electron transport chain (ETC) can lead to a profound hypersensitivity to sevoflurane in children. We studied the sensitivities to sevoflurane, during mask induction and maintenance of general anesthesia, in children presenting for muscle biopsies for diagnosis of mitochondrial disease., Methods: In this multicenter study, 91 children, aged 6 months to 16 years, presented to the operating room for diagnostic muscle biopsy for presumptive mitochondrial disease. General anesthesia was induced by a slow increase of inhaled sevoflurane concentration. The primary end point, end-tidal (ET) sevoflurane necessary to achieve a bispectral index (BIS) of 60, was recorded. Secondary end points were maximal sevoflurane used to maintain a BIS between 40 and 60 during the case, and maximum and minimum heart rate and blood pressures. After induction, general anesthesia was maintained according to the preferences of the providers directing the cases. Primary data were analyzed comparing data from patients with complex I deficiencies to other groups using nonparametric statistics in SPSS v.27., Results: The median sevoflurane concentration to reach BIS of 60 during inductions (ET sevoflurane % [BIS = 60]) was significantly lower for patients with complex I defects (0.98%; 95% confidence interval [CI], 0.5-1.4) compared to complex II (1.95%; 95% CI, 1.2-2.7; P < .001), complex III (2.0%; 95% CI, 0.7-3.5; P < .001), complex IV (2.0%; 95% CI, 1.7-3.2; P < .001), and normal groups (2.2%; 95% CI, 1.8-3.0; P < .001). The sevoflurane sensitivities of complex I patients did not reach significance when compared to patients diagnosed with mitochondrial disease but without an identifiable ETC abnormality (P = .172). Correlation of complex I activity with ET sevoflurane % (BIS = 60) gave a Spearman's coefficient of 0.505 (P < .001). The differences in sensitivities between groups were less during the maintenance of the anesthetic than during induction., Conclusions: The data indicate that patients with complex I dysfunction are hypersensitive to sevoflurane compared to normal patients. Hypersensitivity was less common in patients presenting with other mitochondrial defects or without a mitochondrial diagnosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Purpose of Review: Drug allergy management has previously not been emphasized in the elderly. However, the geriatric population poses several unique characteristics, challenges for drug allergy testing and considerations in the management. Especially in the era of COVID-19, the elderly population is a vulnerable cohort and reviewing the management during this unprecedented time is both timely and relevant., Recent Findings: In recent years, larger scale studies focusing on the epidemiology and prevalence trends of drug allergies among older adults has been summarized in this review. Emphasis on anaphylaxis in the older adults has been studied., Summary: There are many implications of these findings. Epidemiological studies are useful in realizing the burden and spectrum of drug allergies on our healthcare system. It has allowed us to identify certain barriers in drug allergy management and develop ways to overcome these challenges through. Lastly, we have proposed an approach to drug allergy management based on previous studies as well as from our perspective and local experience., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Understand how the clinical history has been used to risk stratify patients reporting a beta-lactam allergy, both in clinical care pathways and predictive models., Recent Findings: Drug allergy clinical care pathways have emerged as a safe and effective method of stratifying patients with a reported beta-lactam allergy into risk categories, with 'low-risk' patients able to proceed straight to direct challenges or test doses. These methods have streamlined antibiotic stewardship policies and penicillin allergy de-labeling. However, how to define 'low-risk' has been subject to much debate. New research has developed predictive models that utilize the clinical history to assess a patient's true risk of beta-lactam allergy., Summary: The clinical history has long been an essential part of drug allergy evaluation and has proven invaluable within the past decade in the development of drug allergy clinical pathways. Evidence-based predictive models that use the clinical history to assess a patient's true risk of beta-lactam allergy offer tremendous promise, but differ in crucial areas such as the populations they study, the predictor variables they use, and the ultimate accuracy they attain. These models highlight key aspects of the drug allergy history and pave the way for future large-scale research., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To review the most recent literature studying the classifications, immunochemistry, and crossreactivity of allergy reactions to cephalosporins., Recent Findings: Over the last five years, research interest has focused on three areas related to cephalosporin allergy: cross-reactivity among cephalosporins and with other beta-lactams; the incidence of adverse reactions in penicillin allergy patients or in reported penicillin allergy labels; and new cephalosporins structures involved in the immunological recognition., Summary: Meta-analysis of a substantial number of studies shows that cephalosporins are safer than previously thought. Evidence supports two main conclusions in that regard. First, there is a relatively low percentage of cross-reactivity between cephalosporins and other beta-lactams with penicillins in penicillin allergy patients. Second, there is a very low incidence of allergy reactions in nonselected as well as in selected penicillin allergy patients when cephalosporins are used prior to surgical intervention.On the other hand, few structures have been discovered related to the immune mechanism of cephalosporin allergy reactions, and these are far from being ready to use in clinical practice., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: An update of the pharmacogenetic risk factors associated with T-cell-mediated delayed hypersensitivity reactions., Recent Findings: Recent HLA associations relevant to our understanding of immunopathogenesis and clinical practice include HLA-B∗13:01 with co-trimoxazole-induced SCAR, and HLA-A∗32:01 with vancomycin-DRESS, for which an extended HLA class II haplotype is implicated in glycopeptide antibiotic cross-reactivity. Hypoactive variants of ERAP1, an enzyme-trimming peptide prior to HLA loading, are now associated with protection from abacavir-hypersensitivity in HLA-B∗57:01+ patients, and single-cell sequencing has defined the skin-restricted expansion of a single, public and drug-reactive dominant TCR across patients with HLA-B∗15:02-restricted carbamazepine-induced SJS/TEN. More recent strategies for the use of HLA and other risk factors may include risk-stratification, early diagnosis, and diagnosis in addition to screening., Summary: HLA is necessary but insufficient as a risk factor for the development of most T-cell-mediated reactions. Newly emerged genetic and ecological risk factors, combined with HLA-restricted response, align with underlying immunopathogenesis and drive towards enhanced strategies to improve positive-predictive and negative-predictive values. With large population-matched cohorts, genetic studies typically focus on populations that have been readily accessible to research studies, but it is now imperative to address similar risk in globally relevant and understudied populations., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

Purpose of Review: Whereas the COVID-19 pandemic has changed our lives worldwide, we hope that vaccination can combat the disease. We propose how to evaluate suspected severe allergic reactions to the vaccines so that as many as possible may be safely vaccinated., Recent Findings: Rare cases of severe allergic reactions after COVID-19 vaccination have been observed, seemingly at a higher frequency than for other vaccines. Few excipients are likely to have caused these reactions. IgE-mediated reactions to polyethylene glycol (PEG) and its derivatives are the most suspected, albeit hitherto unproven, causes. We suggest to make a diagnosis based on skin tests with PEG and PEG derivatives and that these be considered in relation to the decisions required before the first and the second vaccine dose. A vaccine without these excipients is available, but published data about its side effects are limited., Summary: The underlying immunological mechanisms of the rare severe allergic reactions to the COVID-19 vaccines are poorly understood and need to be clarified. Identifying those who have an undiagnosed allergy to PEG and PEG derivatives is crucial before vaccination, and these substances are found in laxatives, cosmetics and in 30% of all our medications today., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: The true exanthematous reactions to drugs in children are rare and overdiagnosed. Drugs may cause exanthema either due to inducing an immune response or because of their interaction with viruses, if drugs are taken in the course of a viral infection. Also, viral infections are very often in children and they can provoke an exanthema which is difficult to differentiate from exanthematous reactions to drugs. Consequently, the majority of children are incorrectly labeled as 'allergic'., Recent Findings: The correct diagnosis of exanthematous drug reactions in children is still an important and hot topic. Most information about the approach and management of drug hypersensitivity in children is applied from available guidelines and consensus statement for adults. Recently, a systematic clinical approach for timely differential diagnosis and management of rashes in children who present a cutaneous exanthema while receiving a drug, is proposed., Summary: It is important to consider the detailed clinical history of appearing and developing exanthematous drug reaction, as well as physical examination which includes the description and the distribution of exanthema and at the end making the appropriate diagnosis. Thus, it could reduce overdiagnosis and promote appropriate procedures, that will prevent the overlabeling of drug hypersensitivity in children., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Antibiotic resistance poses a challenge for Helicobacter pylori eradication treatment. Current guidelines strongly recommend avoiding repeated treatments with the same antibiotic to prevent the emergence of drug resistance. However, for penicillin-allergic patients with recurrent H. pylori eradication failures, avoiding repeated treatments with the same antibiotic severely limits the choice of treatment., Patient Concerns: A 47-year-old woman with a penicillin allergy for whom 2 previous levofloxacin and bismuth-based therapies had failed., Diagnosis: H. pylori infection., Interventions: Agar dilution susceptibility testing and gene sequence analysis was performed to confirm levofloxacin susceptibility again. Therefore, we treated her with a 14-day regimen consisting of levofloxacin (500 mg once daily), furazolidone (100 mg twice daily), colloidal bismuth pectin (220 mg twice daily), and esomeprazole (20 mg twice daily)., Outcomes: The patient was successfully treated with a third levofloxacin and bismuth-based regimen., Lessons: Antibiotics included in previous failed therapies need not be eliminated if no antibiotic resistance is found on antimicrobial susceptibility testing., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To estimate the feasibility, acceptability, and safety of outpatient penicillin allergy testing among pregnant women., Methods: We conducted a prospective cohort study at a large academic hospital from March 2019 to March 2020. We recruited pregnant women with a self-reported penicillin allergy who underwent allergy testing between 14 0/7 and 36 6/7 weeks of gestation., Results: Of 127 eligible women pregnant women, 74 (58%, 95% CI 4-67%) accepted allergy testing. Fifty completed or intended to complete allergy testing, yielding a feasibility rate of 68% (95% CI 56-78%). Among the 46 women actually tested (who ranged in age from 18 to 42), 93% (95% CI 68-100%) had a negative test result. A systemic reaction (symptoms consistent with anaphylaxis) occurred in only 2 women (4%, 95% CI 0.5-15%) despite 20 (43%) reporting a severe allergy. No woman suffered an adverse event as a result of allergy testing. In multivariate analysis adjusting for age and parity, women with public insurance had decreased odds of undergoing penicillin allergy testing (adjusted odds ratio 0.24, 95% CI 0.08-0.69)., Conclusion: Outpatient penicillin allergy testing is acceptable and feasible in pregnancy., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: Ocular allergic contact dermatitis is a common yet challenging and frequently misdiagnosed condition. Inappropriate or delayed treatment can contribute to a variety of clinical symptoms such as tearing and itching with signs such as ptosis and cicatricial ectropion, resulting in deterioration of disease, for which the topical medication was originally prescribed to resolve., Recent Findings: Understanding previously unrecognized pathogenic mechanisms involving ocular contact dermatitis has driven new approaches to control the inflammatory process by neutralizing inflammatory mediators and their receptors., Summary: Early diagnosis and removing the antagonizing substance is crucial to manage ocular contact dermatitis. Steroid therapy is usually required to reduce symptoms. As ocular allergic dermatitis often develops in patients using drugs for chronic conditions that necessitate chronic application, it may be difficult at times to discontinue or replace the offending agent.

Background: Nucleotide triphosphate diphosphatase (NUDT15) genetic testing in addition to thiopurine methyl transferase (TPMT) is recommended to reduce the incidence of adverse severe myelotoxicity episodes induced by thiopurines., Objective: We assessed the cost-effectiveness ratio of combined screening for TMPT and NUDT15 defective alleles by genotyping or next-generation sequencing (NGS) using TPMT genotyping as the reference. Because of the genetic differences in thiopurine toxicity, we tested the screening strategies on individuals of Caucasian and Asian descent., Methods: A decision tree compared conventional TPMT genotyping with combined TPMT/NUDT15 genotyping or NGS using a Monte-Carlo microsimulation model of patients with inflammatory bowel disease. The main outcome was the incremental cost-effectiveness ratios (ICER) with effectiveness being one averted severe myelotoxicity requiring hospitalization., Results: The mean estimated cost of the TPMT genotyping for one year is twice in Asian compared with Caucasian patients (980 euro/patient versus 488 euro/patient), and the effectiveness of TPMT genotyping in Caucasian avoided 43 severe myelosuppressions per 10 000 patients over a year compared with 3.6 per 10 000 patients in Asian. Combined TPMT/NUDT15 genotyping compared with TPMT genotyping had an ICER of 7 491 281 euro per severe myelotoxicity averted in Caucasian, compared to 619 euro in Asian. The ICER of the NGS-based screening strategy is disproportionally high compared with genotyping, irrespective of ethnic descent., Conclusion: With a low cost-effectiveness threshold, combined screening for NUDT15 and TPMT defective alleles is cost-effective compared to TMPT screening alone in patients of Asian descent, but is unrealistic from a cost-effectiveness point of view in Caucasians.

Purpose of Review: This review summarizes the current knowledge of the pathogenic mechanisms of biologics-induced anaphylaxis, and the diagnostic and prophylactic strategies in the management of potentially reactive patients, to improve the safety profile of biologics., Recent Findings: The recent knowledge on the topic highlights the involvement of both effector and regulatory mechanisms in the immune response to biological agents. In addition, the impact of biological's immunogenicity on hypersensitivity reactions has been confirmed in a wider number of studies, defining some details about the kinetics of antidrug antibodies development, specifically immunoglobulin G (IgG) and immunoglobulin E (IgE)., Summary: Biological agents may induce anaphylaxis, mainly through the induction of antidrug antibodies. Biologics-related infusion reactions are often clinically consistent with type I hypersensitivity, but IgG antidrug antibodies may also be involved. The immune response toward biologicals is orchestrated by both effector and regulatory T cells. In addition, nonantibody-dependent mechanisms may occur. Among clinicians persists today again a low awareness, not only of the possibility to understand the immunological mechanisms behind anaphylaxis to biologicals but also the opportunity to apply potential strategies for the management of reactive patients aimed to guarantee a safe retreatment.

Purpose of Review: As drug allergy research aims to inform clinical practice, implementation of best practices may be influenced by financial resources required to incorporate new interventions and the resulting clinical and economic returns on those resource investments. The present review summarizes new insights into the economics of drug allergy over the past year., Recent Findings: While considering economic implications of recent drug allergy research, many studies have addressed different contextual factors related to the setting, provider, or outcomes. Advances in technology have enabled specialized allergists to support remote settings through telemedicine consultation. Training opportunities and interdisciplinary approaches to address drug allergy challenges have enabled multiple provider types to play a role in screening, diagnosis, and management. Penicillin allergy testing has been a major focus for many institutions, with several studies focused on de-labeling strategies including confirmatory skin testing and direct oral challenges., Summary: Studies over the past year provide new opportunities for the field of drug allergy research. The focus of current research to capture direct health costs or savings associated with drug allergy interventions demonstrates opportunity for more cost-effective care delivery and opportunity to explore greater benefits to society.

Purpose of Review: Although rare and counterintuitive, hypersensitivity reactions to corticosteroids have been reported since the 1950s. Delayed hypersensitivity reactions following cutaneous exposure (contact allergy) are well understood and principles of testing, as well as cross-reactivity patterns, have been established. In contrast, understanding of immediate hypersensitivity reactions and delayed hypersensitivity reactions after systemic exposure is evolving more slowly. However, progress has been made in the delineating of underlying pathogenic mechanisms and in the development of testing., Recent Findings: IgE-mediated hypersensitivity reactions to corticosteroids have been described. It has been recognized that some, if not all of them, may be due to excipients in steroid formulations. Two excipients, polyethylene glycol and carboxymethylcellulose, seem of particular importance, but cases of reactions to polysorbate 80 and lactose have also been reported. The use of skin testing but also, increasingly, in-vitro methods such as basophil activation test is improving diagnostic accuracy., Summary: The recognition of the role of excipients is leading to a paradigm shift in our approach to immediate hypersensitivity to corticosteroids. Improved access to in-vivo and in-vitro testing will enhance our understanding of true corticosteroid immediate allergy.

Purpose of Review: The purpose of this review is to provide an update on how best to manage the investigation of suspected perioperative hypersensitivity reactions based on recent literature and key publications., Recent Findings: In the past two years, several very important initiatives have been taken in the field of perioperative hypersensitivity. The 6th national audit project in the United Kingdom has provided new knowledge through a series of studies, including a nationwide prospective study, and the European Academy of Allergy and Clinical Immunology has commissioned a position paper with updated recommendations for investigations. Lastly, a large international working group comprising experts in anesthesiology, allergology, and immunology, the International Suspected Perioperative Allergic Reactions group, has published a series of articles providing updates and new insights into several different key areas of perioperative hypersensitivity., Summary: The investigation of perioperative hypersensitivity reactions is highly complex and aims to identify the correct culprit to ensure future avoidance but also to disprove allergy to other suspected culprits, making them available for subsequent anesthesia. To achieve this, close collaboration between anesthesiologists and allergists is called upon to ensure the best possible outcome for the patient.

Up to 30% of patients report at least one antibiotic allergy, but oftentimes these antibiotic allergies are misdiagnosed. In fact, of the 10% of patients reporting penicillin allergies, 90%-98% are not truly allergic. In an era of increasing antibiotic resistance coupled with a limited number of new antibiotics, evaluating antibiotic allergies is critical in providing optimal patient care. Differentiating adverse drug reactions from antibiotic allergies may seem like a daunting task for clinicians and providers, especially in the emergency department, where decisions are made quickly. However, a systemic approach, including medical record review coupled with patient and/or family interview, is vital in managing patients with antibiotic allergies. Inappropriate, alternative antibiotics are frequently chosen due to patient allergies, and data suggest higher rates of broad-spectrum antibiotic use, antibiotic resistance, and poor outcomes as a result. Herein, we review antibiotic selection in patients reporting antibiotic allergies in the emergency department.

Rationale: Adverse drug reactions (ADRs) to iohexol occur infrequently and generally result in good outcomes. This report describes a 51-year-old man suffering from an ADR to iohexol (Omnipaque 300), which proved fatal., Patient Concerns: The patient was admitted to hospital due to intermittent dizziness over 2 years and transient numbness and weakness of the right limbs for 1 week. The patient was investigated using carotid artery angioplasty (CAA), during which the patient suffered a sudden disorder of consciousness and a tonic-clonic seizure leading to status epilepticus. After the CAA, the patient suffered from increasing cerebral edema volume., Diagnoses: Results of digital subtraction angiography and computed tomography angiography performed at another hospital before the CAA suggested severe stenosis of the left internal carotid artery at the spinal C1 level. In the processes of intraoperative and postoperative CAA, the patient developed severe allergic reactions to the contrast agent including epilepsy, brain tissue edema, and renal failure, which were typical according to the 10th edition of the American College of Radiology Manual on Contrast Media (ACR Manual on Contrast Media, Version 10.3, 2017)., Interventions: The patient was treated with antiepileptic, antianaphylactic therapy, and control of blood pressure. Due to rapid and severe brain edema, a decompressive craniectomy was performed on the left side, but it was unsuccessful in reducing brain edema. Subsequently, the patient was started on continuous renal replacement therapy for progressive renal dysfunction., Outcomes: Despite the use of a variety of medical and surgical interventions, it was not possible to control the patient's condition, which gradually declined leading to death, 7 days post-CAA., Lessons: To the authors' knowledge, this represents the 1st case of fatal contrast-induced ADR to iohexol during CAA. Although a variety of preoperative tests for iohexol allergy were performed according to recommendations from the ACR Manual on Contrast Media (Version 10.3, 2017), severe complications related to iodized contrast agent still occurred. If the ADR had been recognized sooner and decompressive craniectomy and continuous renal replacement therapy were applied earlier, it would have improved the patients' prognosis.

Purpose of Review: Immune-mediated adverse drug reactions (IM-ADRs) are many times more common in HIV-infected patients. Usual offending drugs include antiretroviral and antiinfectives, but the burden of specific drug IM-ADRs is population-specific; changing as new and fixed dose combinations enter the market, and drug-resistance patterns demand. This review considers recent literature on epidemiology, mechanisms, clinical management and prevention of IM-ADRs amongst persons living with HIV/AIDS., Recent Findings: Epidemiological studies continue to describe high rates of delayed hypersensitivity to known offenders, as well as similar reactions in preexposure prophylaxis. IM-ADRs to oral and injectable integrase strand transfer inhibitors are reported with expanding use. The clinical spectrum and management of IM-ADRs occurring in HIV-infected populations is similar to uninfected; with exceptions such as a recently described severe delayed efavirenz DILI with high mortality. Furthermore, the context can be unique, such as the lower than expected mortality in a Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) cohort from a HIV/TB high burden setting. Programmatic data showing the near complete elimination of Abacavir drug hypersensitivity syndrome following implementation of HLA-B57:01 screening is a stellar example of how prevention is possible with mechanistic insight., Summary: IM-ADRs remain a challenge in persons living with HIV. The complexities posed by polypharmacy, overlapping drug toxicities, drug interactions, overlap of IM-ADRs with other diseases, limited alternative drugs, and vulnerable patients with advanced immunosuppression with high mortality, necessitate increased use of drug provocation testing, treat-through and desensitization strategies. There is an urgent need for improved diagnostics and predictive biomarkers for prevention, or to guide treat-through, rechallenge and desensitization approaches.

Purpose of Review: Severe cutaneous adverse reactions (SCAR) are relatively uncommon but can be life-threatening. This review focuses on the nonanaphylactic (non-IgE-mediated) phenotypes of drug hypersensitivity, with specific reference to diagnosis and management of acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN)., Recent Findings: Here, we review recent guidelines on optimal supportive care as well as publications of interventional treatment for SJS/TEN, including various immunomodulating therapies, and management strategies for severe ocular disease with the use of amniotic membrane transplantation. In DRESS, long-term autoimmune sequelae are increasingly recognized and modify strategies for treatment of the acute episode. If the causative drug is not apparent from careful inspection of the drug exposure history, in-vitro diagnostics, HLA testing and skin testing before drug challenge testing may be considered and we present an algorithm for investigation of complex cases., Summary: Careful phenotypic analysis of the increasingly complex recognized patterns of SCAR facilitates the enhancement in our understanding of T-cell mediated drug hypersensitivity and allows the improvement of in-vitro diagnostic testing to minimize patient exposure to test substances in all but a very limited number of cases, thereby enhancing safety.

Purpose of Review: Cutaneous drug hypersensitivity reactions (CDHRs) are a complicated area with multiple clinical manifestations and differential diagnoses, requiring differentiated diagnostic measurements and optimized therapeutic management., Recent Findings: Disseminated CDHRs to classical drugs can be classified by a simple algorithm, whereas chemotherapeuticals or biopharmaceuticals may show drug-specific and atypical clinical presentations. Controversies in drug hypersensitivity diagnosis exist about the benefit and accuracy of in-vitro tests. Although skin tests are the best means of detecting sensitization to drugs, methods have not been sufficiently standardized. The necessity for skin tests before performing drug provocation test (DPT) and of prolonged DPTs is discussed in selected patients. If a suspicion has been documented, β-lactam allergy should be excluded. The standard allergy diagnosis is done by an allergist. In case of urgent need because of an infection and low risk according to history, faster delabeling pathways have been developed. There is weak evidence that patients with mastocytosis may have a slightly increased risk of developing immediate-type drug hypersensitivity; however, if considerations are taken, drugs do not have to be withheld for this patient group. There is particular need for improved diagnostic measurements in patients with drug-induced severe cutaneous adverse reactions (SCARs), both identifying the offending drug and detecting individuals at risk. Further challenges encompass appropriate treatments during the acute as well as chronic phase of SCARs., Summary: Recent literature has contributed to our understanding of clinical manifestations and existing controversies and future needs in this area.

Purpose of Review: Nonsteroidal anti-inflammatory drug (NSAID) is one of the most frequently prescribed medications in the medical field, and hypersensitivity to NSAID is a common adverse drug reaction encountered. However, NSAID hypersensitivity presents a variety of symptoms caused by diverse pharmacological and immunological mechanisms., Recent Findings: Owing to the heterogeneity of the disease, a new concept for the classification of NSAID hypersensitivity has recently been proposed to diagnose and manage NSAID hypersensitivity for personalized treatment. Acute and delayed reactions were distinguished in this classification, and identification of symptoms and speculation of putative mechanisms help physicians make the right diagnosis. NSAID-exacerbated respiratory disease is a noticeable phenotype of NSAID hypersensitivity that involves upper airway comorbidities (chronic rhinosinusitis with nasal polyps) as well as asthmatic features. The cutaneous phenotypes of NSAID hypersensitivity occur, and cross-reactivity with other types of NSAID should be considered in establishing a proper diagnosis. Hypersensitivity to a single NSAID can present urticaria/angioedema and anaphylaxis, in which an IgE-mediated immune response is suggested to be a prime mechanism. Management of NSAID hypersensitivity reactions includes avoidance, pharmacological treatment following standard guidelines, and aspirin desensitization., Summary: The classification, diagnosis, and management of NSAID hypersensitivity should be individually reached by identifying its phenotype.

Purpose of Review: This review aims to describe current best practice and recent advances in the use of risk stratification as a tool for drug provocation testing (DPT). In particular, we focus on the testing of unsubstantiated penicillin allergy labels., Recent Findings: The inherent risks of DPT are mitigated through careful selection of patients. A detailed history will elicit features of a potentially severe index reaction, as well as significant patient comorbidities which may increase the risks associated with DPT. Such patients require skin testing and/or in vitro testing prior to consideration for a DPT. However, there is increasing evidence that patients without these features may be able to proceed directly to DPT. This has been demonstrated extensively with unsubstantiated penicillin allergy labels, and a variety of risk stratification models have been employed to identify the 'low-risk' patient. Improved outcomes and reduced cost have been demonstrated with such models without compromising patient safety., Summary: Risk stratification tools may enable well-tolerated and effective 'delabelling' of low-risk patients, with less demand on already scarce resources.

The combination of BRAF and MEK inhibitors is a standard therapeutic option for patients with metastatic melanoma with BRAF-mutated tumors. This type of targeted therapy improved patient survival, having a manageable toxicity profile. Nevertheless, potentially life-threatening severe toxicity as anaphylaxis-like reactions was observed in two reported cases. No confirmatory testing was performed for these two patients. We report a case of anaphylactic reaction to the BRAF inhibitor dabrafenib administered as a first-line treatment. The clinical picture is different compared with the reported cases, with the main life-threatening symptom being severe hypotension. An important feature of our case report is the diagnostic assessment by drug provocation test, which is considered the 'gold standard' investigation for the diagnosis of drug hypersensitivity. Additionally, serum tryptase levels were assessed, and the basophil activation test has been performed as an in-vitro diagnostic test. Elements in favor of both IgE-mediated and non-IgE-mediated reaction were observed, which is suggestive of a complex pathomechanism. This can be evocative for the heterogenous clinical manifestation of the immediate hypersensitivity reactions to BRAF inhibitors. The mechanisms responsible for the reactions should be investigated in future molecular and cellular studies.

Administration of preoperative antimicrobial prophylaxis, often with a cephalosporin, is the mainstay of surgical site infection prevention guidelines. Unfortunately, due to prevalent misconceptions, patients labeled as having a penicillin allergy often receive alternate and less-effective antibiotics, placing them at risk of a variety of adverse effects including increased morbidity and higher risk of surgical site infection. The perioperative physician should ascertain the nature of previous reactions to aid in determining the probability of the prevalence of a true allergy. Penicillin allergy testing may be performed but may not be feasible in the perioperative setting. Current evidence on the structural determinants of penicillin and cephalosporin allergies refutes the misconception of cross-reactivity between penicillins and cefazolin, and there is no clear evidence of an increased risk of anaphylaxis in cefazolin-naive, penicillin-allergic patients. A clinical practice algorithm for the perioperative evaluation and management of patients reporting a history of penicillin allergy is presented, concluding that cephalosporins can be safely administered to a majority of such patients.

Purpose of Review: NSAIDs are the drugs most frequently involved in hypersensitivity reactions (HSR). These are frequently prescribed at all ages. HSR are of great concern and can affect people at any age. These drugs can induce reactions by stimulating the adaptive immune system (IgE or T cell), known as selective responders or more frequently by abnormalities in biochemical pathways related with prostaglandin metabolism. These are known as cross-intolerant. With some exceptions, skin testing and in-vitro studies are of little value in selective responders., Recent Findings: In the last years, several classifications have been provided based on clinical symptoms, time interval between drug intake and appearance of symptoms, response to other nonchemically related NSAIDs and the underlying disease. Based on this classification, several well differentiated categories within each group of entities cross-intolerant and selective responders are now recognized. The most complex groups for evaluation are cross-intolerant in which three major groups exist: NSAIDs exacerbated respiratory disease, NSAIDs exacerbated cutaneous disease and NSAIDs-induced urticaria/angioedema in the absence of chronic spontaneous urticaria. Within the selective responders, there are two mechanisms involved: drug-specific IgE or T-cell effector responses. New entities have been added to this classification like mixed reactions within the cross-intolerant category, that must manifest as anaphylaxis and multiple immediate selective reactions., Summary: The precise evaluation of patients with NSAIDs hypersensitivity following established guidelines will improve not only our understanding but also the management of these entities. As the number of patients affected with NSAIDs is important, further studies are warranted.

Purpose of Review: The aim of the present review is to discuss recent advances supporting a role of paracetamol metabolism in hypersensitivity reactions to this drug., Recent Findings: Recent developments in the identification of novel paracetamol metabolites, as well as in allele frequencies and functional effects of genetic variation leading to the bioavailablity of reactive paracetamol metabolites, have led to the identification of potential pharmacogenomic and metabolomic targets in studies seeking mechanisms involved in hypersensitivity reactions caused by this drug. Particularly relevant are identification of araquidonate metabolites, identification of specific-binding sequences for reactive paracetamol metabolite-protein adducts, and studies on the frequencies and the functional impact of duplication or multiduplication of genes involved in the formation of reactive metabolites, as well as complete gene deletion or deleterious mutations in genes involved in the detoxification of paracetamol reactive metabolites. In addition, recent evidence points to sex, ethnic origin and age as relevant factors in the production of reactive paracetamol metabolites., Summary: High inter-individual variability in the production of reactive paracetamol metabolites exists, and factors leading to increased bioavailability of reactive paracetamol metabolites are being uncovered. Additional research is required to link these factors to paracetamol-induced hypersensitivity reactions.

Purpose of Review: To present the most recent evidence on beta-lactam hypersensitivity reactions in children., Recent Findings: Drug provocation tests (DPTs) are the gold standard when investigating beta-lactam allergy in children and evidence is increasingly supporting DPTs without skin tests as a safe approach when evaluating children with nonimmediate mild reactions to beta-lactams. Of note, data are limited in the adolescent population, and this attitude may not apply to this age group. Standardization of DPT protocols is required in nonimmediate reactions, as many protocols ranging from 1 to 10 days have been described. The optimal duration of DPT is still unknown, with extended protocols providing slightly more sensitivity and possible higher long-term compliance, at the expense of potential side effects associated with prolonged antibiotic use. On the other hand, 1-day DPTs will identify the vast majority of patients, and the rest will only develop a mild rash during a subsequent full treatment. The natural history of beta-lactam allergy in children is not well studied with recent evidence pointing to the resolution of most confirmed beta-lactam allergies after 3 years., Summary: Further studies are needed for the standardization of DPT protocols and to confirm the favourable natural history of beta-lactam drug allergies in children. In addition, multicentric studies are required to confirm the increasingly accepted position of performing DPTs without skin tests in nonimmediate mild reactions to beta-lactams and to further evaluate the possibility of performing DPTs in benign immediate reactions to beta-lactams in children.

Background: Sugammadex is used to reverse the effects of neuromuscular blocking agents in many cases of general anesthesia. However, there are several reports of anaphylaxis after its use. Skin testing is the gold standard for detecting the causative agent of anaphylaxis. However, due to the lack of validated protocols for skin testing with sugammadex, the diagnostic accuracy might be inadequate. Recently, the basophil activation test (BAT) has been established as a tool to detect the causative agent of anaphylaxis with high sensitivity and specificity. However, few studies have investigated the utility of the BAT for sugammadex-induced anaphylaxis., Methods: Eight patients who presented with immediate hypersensitivity to sugammadex during general anesthesia were included in this study. We conducted skin tests to confirm the diagnosis of sugammadex-induced anaphylaxis. Twenty-one sugammadex-naive individuals who had a negative skin test for allergy to this drug were enrolled as controls. Basophils were selected on a CD3/CRTH2 gate and labeled with CD63 and CD203c., Results: The ratios of activated basophils in the patients were much higher than those in controls: the median values of areas under the curves in the patients and controls for CD203c were 1,265,985 (95% confidence interval [CI], 77,580-5,040,270) and 116,325 (95% CI, -268,605 to 232,690), respectively (Mann-Whitney U test, P < .01), and the areas under the curves in the patients and controls for CD63 were 788,647 (95% CI, 120,285-3,523,410) and 220,005 (95% CI, -50,346 to 404,680), respectively (Mann-Whitney U test, P < .01). The patients, but not controls, demonstrated clear dose-dependent CD203c upregulation. This was also true for CD63. In the case of CD203c, the sensitivity of the BAT for sugammadex was 88% (95% CI, 47%-100%), and specificity was 100% (95% CI, 84%-100%), while sensitivity and specificity for CD63 were 75% (95% CI, 35%-97%) and 100% (95% CI, 84%-100%), respectively., Conclusions: The BAT seems to have comparable accuracy to skin tests for the diagnosis of sugammadex-induced anaphylaxis. For this purpose, both CD203c and CD63 can be used to detect activated basophils.