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The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available.

Drug-induced allergy (DIA), an unexpectedly triggered side effect of drugs used for therapeutic purposes, is a serious clinical issue that needs to be resolved because it interrupts the treatment of the primary disease. Since conventional allergy testing is insufficient to accurately predict the occurrence of DIA or to determine the drugs causing it, the development of diagnostic and predictive tools for allergic reactions is important. We demonstrated a novel method, termed high-sensitive allergy test (HiSAT), for the rapid diagnosis of allergy (within 1 hr; with true-positive diagnosis rates of 89% and 9% for patients with and without allergy-like symptoms, respectively). HiSAT analyzes the cell kinetics as an index against chemotactic factors in a patient's serum, as different from the diagnosis using conventional methods. Once allergy has occurred, HiSAT can be used to determine the causative medicine using culture supernatants incubated with the subject's lymphocytes and the test allergen. This test is more efficient (60%) than the lymphocyte transformation test (20%). Furthermore, in HiSAT, cell mobility significantly increases in a dose-dependent manner against supernatant incubated with lymphocytes from a subject with pollinosis collected at a time when the subject is without allergic symptoms and the antigen. The result demonstraed that HiSAT might be a promising method to rapidly diagnose DIA or to determine with high accuracy the antigen causing allergy., Competing Interests: The authors have declared that no competing interests exist.

Periprocedural or perioperative anaphylaxis is rare, with an estimated incidence of 1 in 10,000 to 40,000 sedation cases. During such procedures, patients are often exposed to numerous medications, such as antimicrobials, neuromuscular blocking agents, sedative and/or hypnotics, and opioids. The most commonly implicated agents include antibiotics (in the United States) and neuromuscular blocking agents (in Europe). In this article, we explore the differential diagnosis and laboratory investigation of a case of periprocedural anaphylaxis.

Background: Penicillin allergy is frequently reported. In pregnant women, reported penicillin allergy is associated with negative health outcomes and suboptimal group B streptococcal prophylaxis. For individuals having penicillin allergy, skin testing followed by an observed oral challenge is recommended. Previous data indicate a low risk of adverse reaction with skin testing in pregnant women, but the subsequent oral challenge was not routinely pursued., Objective: To determine whether skin testing followed by the outpatient oral challenge is tolerated by pregnant women., Methods: We conducted a retrospective review of all pregnant women who underwent penicillin allergy evaluation at an outpatient allergy and clinical immunology clinic. The patients underwent oral amoxicillin challenges based on the discretion of the allergy provider. We evaluated the index reaction history, skin test results, oral challenge results, and subsequent antibiotic exposure., Results: A total of 46 pregnant women underwent skin testing without adverse reactions, of whom 44 patients (95.6%) received negative results. A total of 18 women (39%) completed an oral challenge without adverse reactions. Patients challenged vs not challenged did not differ in patient age, gestational age, latency since index reaction, or reaction history risk level. Notably, 28 women received intrapartum antibiotics. There was no difference in intrapartum antibiotic administration between those who did or who did not complete an in-office oral challenge (P = .90)., Conclusion: Penicillin skin testing and oral challenge in pregnant women can safely be performed in the outpatient setting. There was no difference in the intrapartum antibiotic use between women who were and those who were not challenged. Further research is needed to determine the utility of oral challenge in pregnant patients., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Basophil activation test (BAT) and immunoassays are the most widely used in vitro tests to diagnose IgE-mediated allergic reactions to penicillin. However, studies to determine if one test is interdependent from another are limited., Objective: The present study aimed to measure the agreement between BAT and immunoassay in diagnosis of penicillin allergy., Method: BAT was performed using penicillin G (Pen G), penicillin V (Pen V), penicilloyl-polylysine (PPL), minor determinant mix (MDM), amoxicillin (Amx) and ampicillin (Amp) in 25 patients. Immunoassay of total IgE (tIgE) and specific IgE (sIgE) antibodies to Pen G, Pen V, Amx and Amp were quantified. Skin prick test (SPT) using PPL-MDM, Amx, Amp and Clavulanic acid were also performed., Results: Minimal agreement was observed between BAT and immunoassay (k=0.25). Of two BAT-positive patients, one patient is positive to Amx (59.27%, SI=59) and Amp (82.32%, SI=82) but sIgE-negative to all drug tested. This patient is also SPT-positive to both drugs. Another patient is BAT-positive to Pen G (10.18%, SI=40), Pen V (25.07%, SI=100) and Amp (19.52%, SI=79). In sIgE immunoassay, four patients were sIgE-positive to at least one of the drugs tested. The sIgE level of three patients was between low and moderate and they were BAT-negative. One BAT-positive patient had a high level of sIgE antibodies (3.50-17.5kU/L) along with relatively high specific to total IgE ratio ≥0.002 (0.004-0.007)., Conclusions: The agreement between BAT and immunoassay is minimal. Performing both tests provides little increase in the sensitivity of allergy diagnosis work-up for immediate reactions to penicillin., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Drug allergies are reactions within the context of drug hypersensitivity reactions, which are caused by immunological mechanisms due to a previously sensitising drug. Beta-lactam antibiotics (BLA) are the leading agents causing drug hypersensitivity reactions in children. The aim of this study is to evaluate the diagnostic importance of in vivo and in vitro diagnostic tests in children with suspected immediate-type BLA hypersensitivity and to investigate the frequency of their use for the final diagnosis., Methods: Patients admitted to the Outpatient Clinic of Division of Paediatric Allergy and Immunology with suspicion of immediate-type BLA hypersensitivity between December 2014 and December 2018 were investigated. Patients with a history of immediate reactions to BLA were examined by performing drug specific IgE, skin prick tests, intradermal tests and drug provocation tests (DPT)., Results: During the study period, 148 patients were admitted to our clinic with suspected immediate-type BLA hypersensitivity. Forty-eight patients completed all assessment steps and were enrolled in the study. It has been shown that 27 patients did not have drug allergy. BLA hypersensitivity was proven in 21 patients by using in vivo test algorithm. More than half of the patients were diagnosed via skin tests with culprit drug., Conclusion: Allergy work-up should be performed in patients with immediate reactions to BLA. A skin test can demonstrate BLA hypersensitivity in most patients. Thus, skin tests should be performed prior to the drug provocation test., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Summary: Adverse reactions to iodinated contrast media (ICM) are reported in 1%-3% of diagnostic procedures. They represent a relevant problem involving patients' safety as well as relevant costs for healthcare systems. Premedication with antihistamines and corticosteroids is still widely used, but evidence of its efficacy is lacking and there is a risk for under-estimation of possible severe adverse reactions to ICM in those who undergo premedication. Data from 98 patients with a previous reaction to ICM that consecutively referred to our unit between 2015 and 2018 were retrospectively analyzed. They underwent an allergologic workup comprehending skin tests and drug provocation tests (DPT) with ICM. The skin test showed a very high negative predictive value (NPV) compared to DPT in patients with a previous immediate adverse reaction, while the NPV in patients with a previous delayed adverse reaction was lower. After completion of the allergologic workup, 94 patients (95.9%) could tolerate a DPT with the culprit or alternative ICM. Subsequently, 90 patients were reached by phone to assess if they had been re-exposed to ICM for radiologic procedure. Thirty-nine patients had been re-exposed, without any premedication in 13 cases: 12 of them had tolerated the ICM, while one reacted again despite a negative DPT with the same ICM. Overall, the NPV of this protocol was elevated (92.3%) for patients undergoing DPT and subsequent exposure to the same ICM in a real-life setting. Collaboration between the prescribing physician, the radiologist and the allergist, and an accurate allergologic workup are essential to ensure maximum safety for the patient.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in children and can frequently cause hypersensitivity reactions. Rates of confirmed NSAID hypersensitivity (NSAID-H) in children are low., Objective: To evaluate the results of drug provocation tests (DPTs) with NSAIDs and to evaluate the difficulties encountered in the classification of NSAID-H in children., Methods: The study included patients with suspected NSAID-H who were examined in our clinic between January 1, 2015, and December 31, 2018. Oral provocation tests with NSAIDs were performed and reactions were classified according to the European Academy of Allergy and Clinical Immunology position paper on NSAID-H., Results: A total of 243 patients (57.2% male patients) presented with suspected NSAID-H during the study period. Of these, 168 patients (69.1%) had a history of reaction to ibuprofen. Isolated skin involvement was the most frequent symptom (86%). A total of 238 DPTs were performed with the suspected agents and 34 had positive results. The families of 12 patients refused provocation testing with the suspected agent or aspirin and these patients could not be diagnosed. Of the 231 patients, 47 patients (20.3%) received a diagnosis of NSAID-H. Twenty patients with NSAID-H could not be classified because their guardians did not consent to further testing with aspirin., Conclusion: Performing diagnostic tests is important in patients with no contraindications. Characterizing these reactions in children can be difficult because of the coexistence of indistinguishable symptoms in their history and DPTs, as well as the need for multiple provocation tests. Therefore, further research is needed on this subject., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Systemic contact dermatitis (SCD) is a broad category of syndromes characterized by a variety of clinical presentations and offending agents. There exists general consensus that SCD and its subcategories are due to type IV (and less commonly type III) hypersensitivity reactions, in which a previously sensitized individual undergoes a cytotoxic CD8 + T-cell response upon systemic reexposure. There are various linked allergens, generally grouped into plants, foods, metals, and medications. Diagnosis is relatively successful through epicutaneous patch testing utilizing standard series and customized panels. Treatment consists of allergen avoidance diets as determined by clinical history and patch testing., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of drug-induced hypersensitivity, called "NSAID hypersensitivity". A confirmative diagnosis is necessary for ensuring drug safety and finding alternative drugs. No reliable test other than direct challenge is diagnostic. An intravenous (IV) aspirin challenge has rarely been tried., Objective: To assess the safety and efficacy of the aspirin IV provocation test., Methods: A retrospective and descriptive study in a hospital. Clinical data were reviewed in patients who had aspirin IV provocation test with lysine aspirin., Results: In 71 patients suspected of having NSAID hypersensitivity, aspirin IV provocation test was performed. Most provocations were performed on the same day. Forty-three (60.6%) showed a positive response to the challenge. The positive reactions were rescued mostly by antihistamines or glucocorticoids and rarely with bronchodilators and epinephrine. Three patients who showed a negative response to the aspirin challenge were shown to have single-NSAID hypersensitivity. For confirmation of NSAID hypersensitivity in these patients, the sensitivity of the IV aspirin provocation test was 93.5%., Conclusions: Aspirin IV provocation test with lysine aspirin on the same day is safe and efficacious for diagnosing NSAID hypersensitivity.

Background: Data are lacking with concern to the prevalence and management of aspirin (ASA) hypersensitivity. Objective: To study the prevalence, different types of reactions, and implications for clinical management of ASA hypersensitivity in a cardiology practice. Methods: We conducted an electronic medical record review of 11,375 individuals, 5052 (44%) in the ambulatory setting, and 6323 (56%) admitted for percutaneous coronary intervention (PCI), from January 2012 to December 2013. Results: The prevalence of ASA hypersensitivity was 1.88% (n = 214). Skin reactions were the most common (40 [19%]), followed by angioedema (10 [4.6%]), respiratory (9 [4.2%]), and anaphylaxis (6 [2.8%]). No records were found for 74 patients (34.5%), and 69 patients (32.2%) were mistakenly labeled as allergic for having gastrointestinal symptoms. Of the 214 patients who had documented ASA hypersensitivity, 108 individuals (50.46%) had coronary artery disease. The medications at discharge were the following: ASA (30 [14%]), thienopyridine (48 [22%]), a combination of ASA and thienopyridine (13 [6%]), anticoagulation only (26 [12%]), and no antiplatelet (97 [43%]). Conclusion: ASA hypersensitivity is often not documented correctly or is often misdiagnosed or not appropriately managed. There is a need for improved management of ASA hypersensitivity, including appropriate referral for ASA desensitization and combating unnecessary avoidance in patients with intolerance due to adverse effects.

Background: Antibiotic allergies, especially penicillin, are the most frequent drug allergy listed in the medical record. Proactive evaluations of antibiotic allergies, particularly penicillin allergies, have been recommended by various specialty societies. Objective: To review the history of the discovery of penicillin, implications of the penicillin allergy label, various delabeling strategies as well as a brief overview of the approach to cephalosporin, fluoroquinolone, and macrolide allergy. Methods: Recent studies on penicillin allergy delabeling and on cephalosporin and fluoroquinolone allergies were reviewed. Results: Although Alexander Fleming is often solely credited with the discovery of penicillin, other scientists were critical to the development of penicillin as a life-saving antibiotic. The vast majority of patients with a penicillin allergy label are not allergic; however, this label results in increased morbidities and mortality. A variety of penicillin delabeling strategies can be used in both the outpatient and the inpatient settings. The role of direct penicillin challenge in patients at low risk is emerging and is the method of choice for children. Patients with an unconfirmed penicillin allergy have a low risk of reacting to cephalosporins. The R1 side chain largely dictates cephalosporin allergy and cross-reactivity. Drug challenge is the preferred method for evaluation of both fluoroquinolone and macrolide allergy. Conclusion: Multiple effective methods are available to delabel patients of common antibiotic allergies. Delabeling patients in a proactive manner can reduce patient morbidity.

Summary: Clindamycin is widely used in the prophylaxis and treatment of infections due to its broad spectrum of antimicrobial activity. Hypersensitivity to clindamycin seems to be not very common (less than 1% of drug-allergic reactions) and it mostly appears as delayed T-cell mediated. For the diagnosis, skin testing is considered to be highly sensitive and rather safe, but cutaneous and systemic reactions have been described. Provocation test is considered the gold standard. However, it includes the possibility of severe reactions. We reported two cases of delayed allergic reaction to clindamycin, confirmed with a positive lymphocyte transformation test, showing this in vitro test like a promising diagnostic method because of its usefulness and safety.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used throughout the world. They are frequently involved in hypersensitivity reactions, which range from local or mild reactions to systemic and severe reactions. Consequently, it is necessary to perform an exhaustive study of patients in order to make an accurate diagnosis, search for safe procedures in the case of severe reactions, and identify alternative treatment options. Various guidelines and protocols address the management of hypersensitivity to NSAIDs, although these vary widely from country to country. The Committees of Asthma, Rhinoconjunctivitis, and Drug Allergy of the Spanish Society of Allergy and Clinical Immunology (SEAIC) propose the present position statement on available options for provocation testing with aspirin/NSAIDs. This document is the fruit of an exhaustive review of current evidence and is based on recent publications addressing the diagnosis of patients with hypersensitivity to NSAIDs and on a consensus-oriented discussion among a group of experts from the SEAIC. The main objective was to draft an easy-toread, practical guideline for health care professionals in specialist areas who assess and manage patients with suspected hypersensitivity to NSAIDs. Furthermore, indications, contraindications, and procedures for oral, bronchial, and nasal provocation tests with aspirin/NSAIDs have been updated.

Introduction and Objectives: Drug provocation tests (DPTs) are the gold-standard method to diagnose non-immediate hypersensitivity reactions (NIHSR) to beta-lactam antibiotics (BL) in children. Our aim was to compare the negative predictive value (NPV) of one-day (short) DPT versus 3-7 days (extended) DPT for the diagnosis of NIHSR to BL in paediatric age. A secondary aim was to compare confidence on drug re-exposure after short and extended negative DPTs., Methods: The occurrence of HSR on drug re-exposure and drug refusal after negative diagnostic DPTs were evaluated in children/adolescents with a history of NIHSR to BL using a questionnaire performed six months to ten years after DPT. Patients were divided into two groups according to the protocol performed: short DPT vs. extended DPT., Results: We enrolled 212 children and adolescents (86 females, 126 males, mean age at DPT 5.52 years, p25=3 years, p75=7.25 years): 69 tested with short DPT, and 143 with extended DPT. The NPV of both types of DPT together was 95.2%. The NPV of short DPT was 97.5% and the NPV of extended DPT was 93.8% (p=0.419). After negative DPT, beta-lactams were refused by carers in 14.75% of the children requiring subsequent treatment, 6.98% in the short DPT group and 18.99% in the extended DPT group (p=0.074)., Conclusions: In our paediatric sample, prolonging drug administration did not increase the NPV of diagnostic DPT for NIHSR to BL or reduce drug refusal. Altogether, the data here reported suggest that, however intuitive, prolonging DPT is not beneficial in the parameters analysed., (Copyright © 2019 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Suspected perioperative allergic reactions are often severe. To avoid potentially life-threatening re-exposure to the culprit drug, establishing a firm diagnosis and identifying the culprit is crucial. Drug provocation tests are considered the gold standard in drug allergy investigation but have not been recommended in the investigation of perioperative allergy, mainly because of the pharmacological effects of drugs such as induction agents and neuromuscular blocking agents. Some specialised centres have reported benefits of provocation testing in perioperative allergy investigation, but the literature on the subject is limited. Here we provide a status update on the use of drug provocation testing in perioperative allergy, including its use in specific drug groups. This review is based on a literature search and experiences of the authors comprising anaesthesiologists and allergists with experience in perioperative allergy investigation. In addition, 19 participating centres in the International Suspected Perioperative Allergic Reaction Group were surveyed on the use of provocation testing in perioperative allergy investigation. A response was received from 13 centres in eight European countries, New Zealand, and the USA. Also, 21 centres from the Australian and New Zealand Anaesthetic Allergy Group were surveyed. Two centres performed provocation routinely and seven centres performed no provocations at all. Nearly half of the centres reported performing provocations with induction agents and neuromuscular blocking agents. Drug provocation testing is being used in perioperative allergy investigation in specialised centres, but collaborations between relevant specialties and multicentre studies are necessary to determine indications and establish common testing protocols., (Copyright © 2019 British Journal of Anaesthesia. All rights reserved.)

Local anesthetics are used throughout the health care system. In the perioperative setting and in other settings of exposure to local anesthetics, true allergy is reported very rarely. We present an unusual case of immediate-type perioperative hypersensitivity to lidocaine with cross-reaction to mepivacaine, which was missed on initial investigation. This case illustrates that lidocaine may be a "hidden allergen" in the perioperative setting and should always be considered a potential culprit in cases of suspected perioperative hypersensitivity. The case also demonstrates that suspected perioperative hypersensitivity requires highly specialized investigation and close collaboration between allergists and anesthesiologists.

Background: There is no perfect agreement on how to perform an allergy workup in suspected beta-lactam (BL)-allergic children, since skin test (ST)-induced pain is often a limitation. The aim of the study was to assess the possibility of reducing the number of ST in children when performing a complete allergy workup for BL hypersensitivity reactions., Methods: A retrospective analysis of all patients referring to the Allergy Unit of the University Hospital of Montpellier (France) with positive responses in immediateand non-immediate-reading ST to a BL over a 16-year period was performed, to determine the positive predictive value (PPV) of ST. All pediatric patients with a suspected BL hypersensitivity were skin-tested with the suspected drug only, during the following 54 months., Results: A total of 319 patients reporting 328 BL reactions were included in the retrospective study. The PPV of ST for the reported drug was of 99.4%. Based on the results, the number of patients to include in the prospective study was estimated to be 101. In the prospective study, 229 children were included. We diagnosed a BL hypersensitivity in 12 children (5.2%): Diagnosis was reached in 6 (50.0%) through ST (delayed reading for all) and in 6 through drug provocation test (DPT)., Conclusion: ST with BL should therefore be performed as a screening test, before DPT, and testing only the suspected drug may be sufficient when dealing with children., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Introduction: Beta-lactams are the most frequently used antibiotics in pediatric age. Anaphylactic reactions may occur and need to be properly studied, but studies in children are scarce., Objective: Characterization of case reports of anaphylaxis in children referred to an allergy department with suspected beta-lactams hypersensitivity., Materials and Methods: Retrospective analysis of all children referred to our Drug Allergy Center with suspected beta-lactams hypersensitivity between January 2011 and December 2016. Description of the drug allergy work-up performed studied according to standardized diagnostic procedures of ENDA/EAACI, including specific-IgE assay, skin prick and intradermal tests and diagnostic/alternative drug challenge tests., Results: 146 children with suspected beta-lactams hypersensitivity were studied, and in 21 (14.4%) the diagnosis was confirmed. In all of them, except for three children, an alternative beta-lactam was found. In seven children (33.3% of those with confirmed beta-lactams hypersensitivity) anaphylaxis was confirmed, and all of them described reactions with cutaneous and respiratory or gastrointestinal involvement. The culprit drug was amoxicillin in six and flucloxacillin in one. In this sample, we also performed oral challenge with cefuroxime, being negative in all cases. Almost all cases of confirmed anaphylaxis (six from seven cases) were IgE mediated, with positive skin tests despite negative serum specific-IgE., Conclusions: Allergic reactions to beta-lactams, although rare in children, require a detailed clinical history and a specialized drug allergy work-up to allow a correct diagnosis as well as to avoid the possibility of a potential life-threatening reaction and provide alternative drugs., (Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Systemic contact dermatitis (SCD) describes a hypersensitivity reaction following systemic re-exposure of the inciting allergen in previously sensitized individuals. Plants, drugs, and metals are the most common causes of SCD. In individuals with obstinate dermatitis, it is imperative to deliver history-focused patch testing with subsequent avoidance and elimination of the compound.

Consumer products and topical medications today contain many allergens that can cause a reaction on the skin known as allergic contact dermatitis. This review looks at various allergens in these products and reports current allergic contact dermatitis incidence and trends in North America, Europe, and Asia. First, medication contact allergy to corticosteroids will be discussed along with its five structural classes (A, B, C, D1, D2) and their steroid test compounds (tixocortol-21-pivalate, triamcinolone acetonide, budesonide, clobetasol-17-propionate, hydrocortisone-17-butyrate). Cross-reactivities between the steroid classes will also be examined. Next, estrogen and testosterone transdermal therapeutic systems, local anesthetic (benzocaine, lidocaine, pramoxine, dyclonine) antihistamines (piperazine, ethanolamine, propylamine, phenothiazine, piperidine, and pyrrolidine), topical antibiotics (neomycin, spectinomycin, bacitracin, mupirocin), and sunscreen are evaluated for their potential to cause contact dermatitis and cross-reactivities. Finally, we examine the ingredients in the excipients of these products, such as the formaldehyde releasers (quaternium-15, 2-bromo-2-nitropropane-1,3 diol, diazolidinyl urea, imidazolidinyl urea, DMDM hydantoin), the non-formaldehyde releasers (isothiazolinones, parabens, methyldibromo glutaronitrile, iodopropynyl butylcarbamate, and thimerosal), fragrance mixes, and Myroxylon pereirae (Balsam of Peru) for contact allergy incidence and prevalence. Furthermore, strategies, recommendations, and two online tools (SkinSAFE and the Contact Allergen Management Program) on how to avoid these allergens in commercial skin care products will be discussed at the end.

Background: A spurious label of penicillin allergy (Pen-A) negatively impacts on antibiotic stewardship and health care costs. Recent studies have proposed a guideline-steered direct penicillin challenge without undertaking allergy tests when "true allergy" is unlikely., Objective: To critically analyze Pen-A clinical presentation, perform risk stratification, and determine clinical predictors for "true allergy.", Method: Data were extracted retrospectively from clinical and electronic patient records., Results: A total of 231 patients (M = 82; F =149; mean age 51.22 [standard deviation ± 18.07] years) were analyzed. Based on clinical history, patients were categorized as likely type I hypersensitivity reaction (HSR) (n = 27), likely type IV HSR (n = 65), indeterminate (n = 111), and HSR unlikely (n = 28). Based on an index reaction and comorbidities, patients were classified into "low risk" (n = 143) and "high risk" (n = 78). Pen-A was excluded in 74% of patients assessed having likely type I HSR, 91% with likely type IV HSR, 93% of indeterminate, and 100% of HSR unlikely patients. The negative predictive value for successful delabeling in the "low risk" group was 94% (odds ratio [OR] = 2.9; P = .02). Predictors for "true Pen-A" were history of anaphylaxis (OR = 30.6; P < .001), hospitalization (OR = 7; P < .001), ≤5 years since the index reaction (OR = 3; P = .04)., Conclusions: Systematic clinical characterization and risk stratification has an important role in Pen-A delabeling. These data provide proof of concept for a guideline-based selection of patients labeled with Pen-A for a direct penicillin challenge. Patients in the "low risk" group seem suitable for this intervention, although a rigorous prospective evaluation is needed in a multicenter study., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Unconfirmed penicillin allergy poses substantial public health consequences. The most widely accepted protocol to evaluate penicillin allergy is skin testing followed by an amoxicillin challenge., Objective: To evaluate the safety of direct oral graded challenges to amoxicillin., Methods: A prospective single-blind clinical trial with historical controls of patients ≥7 years old with historical non-life-threatening reactions to penicillin was conducted. Patients received placebo followed by a 2-step graded challenge to amoxicillin. The allergic reaction rate was compared with the rate observed in our previous study that included skin testing and with the currently reported penicillin allergy prevalence in the US population., Results: Of the 155 participants who completed an amoxicillin challenge, 120 patients (77.4%) experienced no reaction whereas 31 patients (20%) experienced nonallergic reactions to either placebo (n = 16) or amoxicillin (n = 15). Four patients (2.6%) developed mild allergic reactions. Significantly (P = .03) fewer patients (4 of 155, 2.6%, 95% confidence interval [CI]: 1.0%, 6.5%) were determined to be allergic compared with 14 of 170 subjects (8.2%, 95% CI: 5.0%, 13.4%) in our previous study where patients were determined to be allergic based on either positive skin tests (n = 11) or allergic challenge reactions after negative skin tests (n = 3). This 2.6% reaction rate was also significantly less than the 10% reported US prevalence of penicillin allergy (P = .003)., Conclusions: Placebo-controlled oral graded challenges to amoxicillin without prior skin testing may be safe for patients ≥7 years old with non-life-threatening historical reactions to penicillin. Amoxicillin can be tolerated by the majority of patients with self-reported penicillin allergy., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: β-Lactam antibiotics are the most common trigger of reactions in children with most of them being nonimmediate (85.5%), but proven allergy after the allergological workup is between 7% and 10%. There is no agreement on how to perform the provocation tests in these types of hypersensitivity reactions., Objective: To determine whether or not repeated doses of the β-lactams are required to reproduce a nonimmediate reaction in children., Methods: This is a retrospective observational study. We included children under 14 years who were referred for a nonimmediate reaction to β-lactams. All patients underwent a 1-day hospital provocation and were kept under observation at home during the following days for at least the time elapsed between the first dose and the symptoms of the index reaction. If no reaction was triggered, the patient resumed the provocation at home with 2 daily therapeutic doses for an equal of interval time., Results: Ninety-seven patients were included in the study. A positive reaction was recorded in 14 of them (14.4%). The short hospital provocation triggered 3 immediate reactions and 8 delayed reactions. The home rechallenge developed 1 immediate reaction and 2 delayed reactions., Conclusions: Nonimmediate reactions to β-lactams in children may be triggered with a 1-day provocation test. We suggest to perform a 1-day provocation test followed by an observational period of at least the time interval of the index reaction. If this challenge is negative, an extended home provocation could subsequently be carried out., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Unverified penicillin allergy label has negative health implications. To address this, several delabeling methods have been proposed., Objectives: To appraise the long-term outcomes of the penicillin allergy evaluation in ambulatory patients, focusing on subsequent use of penicillins in individuals found not allergic. A secondary objective was to examine the consistency between the evaluation's recommendations and the allergy label., Methods: A retrospective medical records review and phone survey were carried out in ambulatory patients who were evaluated for suspected penicillin allergy in our allergy unit. Patients with an uneventful oral challenge test (OCT) were interviewed regarding subsequent use of penicillins. Medical records were examined for antibiotic prescriptions and purchases. The records were also investigated for existing/erased penicillin allergy label and its consistency with the allergy evaluation., Results: Six hundred thirty-nine patients with an uneventful OCT were available for the survey. During a 56-month follow-up, 70% (447 patients) had used penicillins at least once. One hundred ninety-two patients (30%) did not use penicillins. The main reason for not using penicillins was lack of a clinical indication. Three hundred thirty-five patients (51.22%) carried a penicillin allergy label in their electronic medical file in spite of an uneventful OCT., Conclusions: Penicillin allergy annulling via OCT has proven to be effective. Most of the patients who previously avoided penicillins have reused penicillins safely., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: True corticosteroid (CS) allergy is rare. Instead, many patients may be allergic to excipients found in various CS preparations. Excipient testing is frequently overlooked. It might lead to unnecessary CS avoidance or dangerous re-exposure., Objective: The objective of this study was to evaluate the clinical characteristics and frequency of excipient allergy in patients with confirmed type I hypersensitivity to systemic CS preparations., Methods: Patients with a confirmed diagnosis of allergy (positive skin test or drug provocation test [DPT]) or tolerance (negative DPT to CS) over the past 10 years were studied. Patient characteristics, index CS, route of administration, clinical indications, symptoms of index reaction, and outcomes of CS/excipient allergy testing were analyzed., Results: Sixty-four patients underwent CS allergy testing. True CS allergy was confirmed in 9 of 64 (14%) patients. The majority (5/9, 56%) with positive skin tests or DPT were actually allergic to the excipients (2 to carboxymethylcellulose and 3 to polyethylene glycol) rather than the CS. Respiratory manifestations were significantly associated with confirmed allergy (odds ratio = 6.79 [95% confidence interval = 1.36-34.03], P = .02)., Conclusions: Patients with respiratory manifestations were significantly more likely to be truly allergic. CS allergies are rare and may be overdiagnosed without excipient testing. We suggest the use of Carmellose eye drops as a readily available source of carboxymethylcellulose for testing and propose a comprehensive diagnostic algorithm for suspected CS allergy., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Neuromuscular blocking agents (NMBAs) are the main agents involved during perioperative immediate hypersensitivity. The etiological diagnosis (IgE-mediated allergy vs nonallergy) is linked to the clinical presentation together with tryptase and histamine levels and skin test results. The role of basophil activation test (BAT) needs to be better defined in this setting., Objectives: To assess the role of BAT compared with the results of skin testing in 31 patients experiencing immediate NMBA hypersensitivity and compare skin test results and BAT performances in the identification of alternative NMBAs., Methods: Histamine and tryptase levels were quantified. Anesthetic drugs, including NMBAs, were skin-tested. Basophil CD63 and CD203c expressions were measured in response to serial dilutions of the different NMBAs., Results: Allergy and Nonallergy groups involved 19 and 12 patients, respectively. Circulating histamine and tryptase levels were significantly increased in allergic patients. In the Allergy group, while skin test results were positive in 100% (19 of 19) of the cases, BAT positivity to the culprit NMBA reached 78.9% (15 of 19) when combining CD63 and CD203c. NMBAs cross-reactivity was identified through skin testing and BAT in 36.8% (7 of 19) and 26.3% (5 of 19) of the cases, respectively. The concordance (culprit and cross-reactive NMBAs) between skin tests and BATs was between 73.6% (14 of 19) and 100% (19 of 19) for each NMBA. Negative skin-tested NMBAs were uneventfully used in 7 NMBA-allergic patients. In the Nonallergy group, skin test results were negative in 100% of the cases while BAT result was positive once (CD63 upregulation)., Conclusion: In our technical conditions, BAT does not replace skin testing in the assessment of NMBA allergy., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Summary: Anticonvulsants are among the drugs most commonly involved in cutaneous adverse drug reactions (CADRs). Eslicarbazepine is a new anti-epileptic drug, chemically related to carbamazepine but with a more favorable safety profile. We report the clinical case of a woman who developed a skin rash on day 10 of eslicarbazepine with further exacerbation with eosinophilia on day 2 of carbamazepine. Epicutaneous tests were positive with eslicarbazepine.