Rostrum Managing Nut Allergy: A Remaining Clinical Challenge Philippe A. Eigenmann, MD a , Gideon Lack, FRCPCH b , Angel Mazon, MD c , Antonio Nieto, MD c , Diab Haddad, MRCPH d , Helen A. Brough, FRCPCH b , and Jean-Christoph Caubet, MD a Geneva, Switzerland; London and Chertsey, United Kingdom; and Valencia, Spain 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. Ó 2016 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2017;5:296-300) Key words: Peanut allergy; Tree nut allergy; IgE testing; Cross- reactivity In the first half of the 20th century, milk, cereal grains, and hen’s egg were reported as the most common food allergens. 1 Reactions to nuts were then mostly anecdotal, such as in the report from 1931 by Vaughan in which peanut allergy is reported as a cross-reacting legume eliciting urticaria in a young female patient. 2 Systemic allergic reactions to tree nuts (commonly included in the tree nut family are almond, Brazil nut, cashew nut, hazelnut, walnut, pecan, pistachio, and macadamia nut) but also mostly to peanut have been increasingly reported only in the last quarter of the 20th century, leading to the concept of the “peanut allergy epidemic.” 3-5 To a large part, peanut and tree nut allergy has gained public attention due to the severity of the reactions. These foods have been identified as the main culprits of fatal or near-fatal reactions in 2 successive reports published in the United States in the late 1980s and early 1990s. 6,7 Strikingly, most of these children had a reaction to more than 1 nut. This led to the general recom- mendation in peanut- or tree nuteallergic patients to avoid all types of nuts, often regardless of positive or negative test results. In addition, preventive avoidance of nuts never eaten was advised although clear scientific evidence was lacking. 8 Overall, safety has been advocated also to avoid reactions by cross-contaminating nuts. These recommendations have largely contributed to the number of children avoiding all nuts in the community. Evi- dence is lacking as to whether extended or targeted avoidance influences the quality of life of these patients or their risk of future reactions. a Pediatric Allergy Unit, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland b King’s College London, Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, Division of Asthma, Allergy and Lung Biology, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom c Children’s Hospital La Fe, Pediatric Pulmonology and Allergy Unit, Instituto de Investigacion La Fe, Valencia, Spain d St Peter’s Hospital, Chertsey, United Kingdom Conflicts of interest: P. A. Eigenmann has consultancy arrangements with Micro- testDX, DBV technologies, Nestlé, Gesellschaft zur Förderung der dermatologi- schen Forschung und Fortbildung e.V., Danone, and Novartis; is employed by the University Hospitals of Geneva; has provided expert testimony for the European Food Safety Authority (EFSA); has received 1 or more grants from or has 1 or more grants pending with the Swiss National Science Foundation, the Ulrich Muller Gierock Foundation, and Leti; has received 1 or more payments for lecturing from or is on the speakers’ bureau for ThermoFisher and Sodilac; has received royalties from UpToDate and Elsevier; owns stock/stock options in DBV Technologies; and has received 1 or more payments for travel/accommodations/ meeting expenses from the European Academy of Allergy and Clinical Immu- nology (EAACI). G. Lack has been supported by 1 or more grants from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Food Allergy & Research Education (FARE; contribution to NIAID contract/grant), Medical Research Council (MRC) & Asthma UK Centre (contribution to KCL Division of Asthma, Allergy & Lung Biology of which Paediatric Allergy is a part), the UK Department of Health through National Institute for Health Research (NIHR) (Biomedical Research Centre Award to Guy’s & St. Thomas’ National Health Service [NHS] Foundation Trust), the National Peanut Board (support for Paediatric Clinical Trials Unit), and the UK Food Standards Agency and has received 1 or more grants from or has 1 or more grants pending with the MRC (contribution to KCL Division of Asthma, Allergy & Lung Biology of which Paediatric Allergy is a part). A. Nieto is a board member for Novartis; has consultancy arrangements with Novartis, Diater, and Meda; and has received 1 or more payments for lecturing from or is on the speakers’ bureau for Novartis, Meda, Uriach, Leti, and Diater. H. A. Brough has consultancy arrangements with MEAD Johnson Nutrition and Nutricia; has received a FARE Charity grant and has received 1 or more grants from or has 1 or more grants pending with the Immune Tolerance Network and the NIH; has received 1 or more payments for lecturing from or is on the speakers’ bureau for Meda Pharmaceuticals, Thermo Scientific, and Nutricia; and has received royalties from Wiley Blackwell Ltd. J.-C. Caubet has received support for travel from Thermofisher and has received 1 or more grants from or has 1 or more grants pending with the Muller Foundation. The rest of the authors declare that they have no relevant conflicts of interest. Received for publication January 14, 2016; revised July 16, 2016; accepted for publication August 22, 2016. Available online October 25, 2016. Corresponding author: Philippe A. Eigenmann, MD, Pediatric Allergy Unit, Uni- versity Hospitals of Geneva, 6 rue Willy-Donze, 1211 Geneva 14, Switzerland. E-mail: Philippe.Eigenmann@hcuge.ch. 2213-2198 Ó 2016 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaip.2016.08.014 296