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Oral allergy syndrome or pollen food allergy syndrome (PFAS) represents a common clinical conundrum when the reported trigger food is a tree nut (usually almond or hazelnut) or peanut. The PFAS may give rise to uncertainty about the potential severity of the future reactions, indications for prescribing epinephrine, and the extent of the necessary dietary avoidance. As a food allergy, secondary to cross-reactivity with airborne pollen, PFAS usually manifests toward the end of the first decade of life as contact urticaria of the oropharyngeal mucous membranes. Molecular allergology facilitates diagnosis and risk stratification by establishing the profile of sensitization. Exclusive sensitization to pathogenesis-related proteins family 10 (PR10) and profilins indicates that signs and symptoms are due to PFAS, whereas sensitization to seed storage proteins with or without sensitization to PR10 and profilins may indicate a more severe primary nut allergy phenotype. Management relies on avoidance of the specific nut trigger, advice on the likelihood of more severe local or systemic symptoms, and treatment of reactions according to the severity. Future studies are needed to better delineate the risk of systemic reactions in individuals with nut PFAS and to establish the role of food or pollen allergen immunotherapy for the prevention or moderation of this condition., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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

Background: Nut allergic patients are often IgE sensitized to other nuts/seeds and need multiple oral food challenges (OFCs) before the safe nuts can be introduced in the diet. However, OFCs are time-consuming and risky procedures., Objective: To assess the utility of the basophil activation test (BAT) to predict the allergic status and reduce the need for an OFC in children with 1 or more nut or seed allergies., Methods: Participants in the Pronuts study recruited at the Geneva and the London centers were tested on the BAT to hazelnut, cashew nut, sesame, almond, and peanut, Ara h 1, Ara h 2, Ara h 6, using FlowCAST, a commercially available BAT kit, and flow cytometry., Results: The BAT to hazelnut, cashew nut, sesame, almond, and peanut discriminated between allergic and nonallergic children, to the respective nut or seed. The optimal allergen concentration and their optimal, positive, and negative cutoffs were identified for the BAT and the other tests, for each nut and seed. Using the BAT as a second step in the diagnostic process, after equivocal skin prick test and IgE to extracts and components, reduced the number of total OFCs by 5% to 15% and positive OFCs by 33% to 75% (except for hazelnut) with 0% false-negatives and a diagnostic accuracy of 96% to 100%., Conclusion: The BAT proved to be a useful diagnostic tool, used in a stepwise approach, to predict the allergic status and reduce the number of OFCs in the Pronuts study participants with at least 1 nut allergy willing to consume selected nuts., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Diagnosis of hypersensitivity (HS) reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in children is complex. The real prevalence of NSAID HS remains unknown because a drug provocation test (DPT) is not always performed with the culprit NSAID., Objective: To describe and compare the diagnostic workup among different European centers and to find out the real proportion of NSAID HS by performing a DPT with the culprit drug., Methods: We retrospectively collected data from children (0-10 years) and adolescents (10-18 years) with a history of NSAID reactions and who underwent a complete allergy workup including DPTs with the culprit in 6 different pediatric centers: Belgrade, Florence, Geneva, Madrid, Porto, and Rome., Results: A total of 693 children with a history of NSAID reactions were enrolled, and a total of 526 DPTs were performed with the culprit NSAID. The diagnosis of NSAID HS was confirmed in 19.6% (103 of 526) of children by performing a DPT with the culprit drug. The major differences in the allergy workup among the 6 centers concerned the duration of the DPT and the practical use of skin tests for diagnosing NSAID HS. In addition, the use of acetyl salicylic acid to differentiate single reactor or cross-intolerance patients is not common, except in Spain., Conclusion: The value of this study is that although different approaches are used around Europe to diagnose NSAID HS, we found that the percentage of confirmed NSAID HS is less than 20%. This highlights the importance of the DPT in confirming or excluding NSAID HS in the pediatric population., (Copyright © 2019. Published by Elsevier Inc.)

Peanut is an allergenic legume that can cross-react with other plant-based foods, notably other legumes and tree nuts. Peanut-allergic individuals can be both cosensitized and coallergic to such items, requiring foresight when eliciting a clinical history of a reaction, in the diagnostic evaluation of such allergies, and in the counseling of patients as to food avoidances after a diagnosis is made. Legume allergens belong to the Fabaceae family and encompass the cupin, prolamin, PR-10, and lipid transfer protein families, which mediate cross-sensitization including that between peanut and tree nut. Among legumes, the most common patterns of clinical cross-reactivity are between peanut and lupine, peanut and soy, as well as chickpea and lentil, though this is highly dependent on geography and prevalence of these foods in the diet. Issues of cross-sensitization may exist between peanut and certain tree nuts, as well as among tree nuts though such patterns do not always result in clinically relevant allergy. Molecular diagnostic testing may be a future tool to help parse out the aforementioned patterns, but oral food challenges are still the gold standard for accurate diagnosis. Although potential desensitization treatments have emerged for peanut allergy, these have not been developed for other legumes and most tree nuts, and desensitization to peanut has not proven to have an effect on legume cross-sensitization., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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

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

Background: The drug provocation test (DPT) is considered as the gold standard to diagnose drug allergy and is particularly important in the diagnosis of nonimmediate beta-lactam (BL) allergy in children. The natural history of BL allergy remains unknown., Objective: Our main aim was to evaluate the natural history of nonimmediate BL hypersensitivity and the long-term tolerance acquisition, and our secondary objective was to determine the negative predictive value (NPV) of the DPT following a 2-day protocol., Methods: Children developing a benign rash while treated by BL were prospectively recruited at the Emergency Department of the Geneva University Hospital from 2006 to 2011 and challenged with the incriminated BL (initial diagnostic drug provocation test [idDPT]) following a 2-day protocol. In case of a positive idDPT, the patients underwent a follow-up drug provocation test (fuDPT) 3 years later. In case of a negative idDPT, we sent a questionnaire to assess tolerance of a subsequent treatment with the incriminated BL., Results: Among the 18 children with a positive idDPT, 16 children (89%) had a negative fuDPT and 2 children developed a benign exanthema. Among those 16 children, 11 tolerated a subsequent treatment with the incriminated BL without any reaction, suggesting natural antibiotic tolerance acquisition. From another point of view, we found that the NPV of the DPT following a 2-day protocol was excellent at 96.7%., Conclusions: Our data strongly suggest that a fuDPT is safe and useful to assess tolerance acquisition in children with a confirmed benign nonimmediate BL allergy. In addition, our results support the use of a short DPT protocol (2 days), which led to a high NPV of 96.7% in our population, with a favorable benefit-risk balance., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Peanut and tree nut allergies have become a public health problem over the last 2 decades. The diagnostic procedure relies on a suggestive history, as well as on evidence of sensitization (skin prick testing and/or specific IgE blood testing), followed in selected cases by a food challenge. Standard IgE tests may be positive to more than 1 nut, due to cross-reactivity (allergens common to several nuts) or cosensitivity (frequently associated positive test results without cross-reactivity). Thus, many patients with a peanut or a tree nut allergy avoid all nuts, relying on positive test results without clinical evidence of reactivity. In addition, coexisting pollen sensitivity may add to diagnostic uncertainty due to potential cross-reactivity between pollens and nuts. In this article, we discuss challenges in diagnosis and clinical management of peanut and tree nut allergy related to cross-reactivity and cosensitization, as well as the avoidance of nuts tested positive to reduce the risk of reactions by cross-contamination. Studies to provide more accurate characterization of genuine clinically relevant cross-reactivity or cosensitivity to multiple nuts are needed., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Cow's milk (CM) and hen's egg allergies are among the most common food allergies in children. With evidence of increasing food allergy prevalence and more persistent disease, it has become vital to improve the management of CM and egg allergies. The ability to tolerate baked milk or egg, such as in a cake or muffin, has been associated with an increased chance of tolerance development. Studies report that about 70% of CM- and egg-allergic children can tolerate baked milk or egg and that incorporating baked milk or egg into the diet is well tolerated. Being able to add baked milk or egg into the diet can also increase quality of life by expanding the diet, boosting nutrition, and promoting inclusion in social activities. There is some debate over how baked milk and egg should be introduced, at home or in a supervised setting. Anaphylaxis and treatment with epinephrine during baked milk or egg challenges have been reported. Study of potential biomarkers to predict tolerability of baked milk and egg, such as serum specific IgE levels and skin prick test wheal diameters, is ongoing. Many parents can reliably report that their CM- or egg-allergic child is already consuming baked goods without symptoms. However, for those who cannot report such tolerance, the most prudent approach is to perform a supervised oral food challenge to determine the tolerability of baked milk and egg. The purpose of this article was to review the pathophysiology, clinical data, and safety of baked milk and egg and provide a practical guide to managing CM allergy and/or egg allergy. Recipes for baked milk and egg challenges and guidance on how to add baked milk and egg if tolerated to the child's regular diet are provided., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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

Atopic dermatitis (AD) is a common skin disease characterized by inflammatory, chronically relapsing and pruritic eczematous flares. Its estimated incidence is 10% to 30% in children. Food allergy has been well documented in approximately one-third of children with a moderate-to-severe AD. Cow's milk, hen's egg, peanut, wheat, soy, nuts, and fish are responsible for >90% of food allergy in children with AD. The incidence and type of food can vary with age. In infants, cow's milk, hen's egg, peanut, and soy and, in older children, wheat, fish, tree nuts, and shellfish are the most common food allergens. Birch-associated foods have also been described as potential triggers of AD in children as well as in adults. The diagnosis of food allergy in AD is currently based on the clinical history, skin prick tests, or blood test screening, followed by an elimination diet and/or standardized oral food challenge. Once an underlying food allergy is confirmed, the avoidance of the incriminated food is generally recommended and usually leads to an improvement of the AD. Follow-up clinical evaluation with a detailed history and tracking of the level of specific IgE to implicated foods are typically used to evaluate the development of clinical tolerance, further confirmed by an oral food challenge., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)