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      Controversies in drug allergy: consensus documents from the world experts

      editorial

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          Abstract

          Drug allergy is an extremely important problem worldwide due to its frequency, potential severity, and consequences. It is also a problem that often provides the opportunity for meaningful interaction between allergist-immunologists and other members of the medical community. This includes primary care physicians as well as other medical and surgical specialists, and these interactions may occur not only in outpatient settings but in hospitals and emergency departments as well. The optimal approach to drug allergy often requires a team approach, and allergist-immunologists must be essential members of that team. It is therefore critical that allergist-immunologists provide the best evidence-based recommendations and care possible for this far-reaching condition. As Editors-in-Chief of the Journal of Allergy and Clinical Immunology: In Practice, the World Allergy Organization Journal, and the Journal of Allergy and Clinical Immunology, we have the opportunity to review many articles on the subject of drug hypersensitivity. In that capacity, we have been struck by the wide geographical variation in the approach to the diagnosis and management of a number of types of drug allergy. Although some of this variation may be necessary due to geographical differences in drug use or host responses, we believe that this variation is an opportunity for quality improvement in the care of drug allergy patients around the world. We felt that the Joint Congress of the American Academy of Allergy, Asthma & Immunology and the World Allergy Organization, which was held in March of 2018 in Orlando, Florida, would provide an excellent opportunity for the three journals to sponsor an international consensus conference to try to address some of the most controversial areas in the field of drug allergy. The outcomes of that meeting are included in current issues of our journals. They represent the work of 54 authors from 26 countries and provide a truly global attempt to address the controversies and practice variation in the world of drug allergy. Published in the Journal of Allergy and Clinical Immunology: In Practice are articles on the subjects of beta-lactam allergy assessment, from both an individual [1] and an institutional [2] perspective, and hypersensitivity reactions to radiographic contrast media [3]. In the Journal of Allergy and Clinical Immunology are articles on in vitro testing for drug allergy [4] and the approach to delayed drug reactions [5]. In each case, current areas of agreement, areas of disagreement, consensus recommendations, and unmet needs are highlighted. An overall perspective and summary of these articles appears in the World Allergy Organization Journal [6]. The editors acknowledge the extraordinary efforts of the co-chairs of this initiative, Mariana Castells and Pascal Demoly. They have skillfully directed all aspects of the project, including topic choices, selection of participants, the organization and running of the in-person meeting, and the coordination and review of the resulting manuscripts. In addition, they have written a superb summary of the various articles and their most important take-away points. This initiative simply would not have been possible without their dedication and inspired leadership. We also express our deep appreciation to all participants and authors who have generously given of their time and expertise without any financial reimbursement. Finally, we thank the Journal of Allergy and Clinical Immunology: In Practice Managing Editor, Dawn Angel, for her invaluable logistical support of this endeavor. We are delighted to have the opportunity to present these extensively researched and thought-out collaborations among the world’s drug allergy experts. We hope these documents will help our clinician readers to provide the most appropriate evidence-based care for the patients they see with drug allergy, including optimal diagnosis, management, and recommendations for future therapy. When options exist, we believe these articles will help practitioners choose the best approach for their particular patients and setting. In addition, we are optimistic that these documents will help allergist-immunologists interact with other members of the health care team to provide optimal drug allergy care on an institutional basis. This series of articles will also help researchers appreciate the unmet needs in the field of drug hypersensitivity and stimulate work as individuals and in collaborations to provide answers to these remaining areas of uncertainty. In this way, we hope these articles will not be an end in themselves but just an important status report toward the ultimate goals of prevention of adverse reactions to drugs to the extent possible and optimizing the quality of care and the quality of life of patients who experience such reactions.

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          Controversies in drug allergy: Testing for delayed reactions

          Controversies exist with regards to in vivo approaches to delayed immunologically mediated adverse drug reactions (ADR) such as exanthem (maculopapular eruption), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome/toxic epidermal necrolysis, and fixed drug eruption. In particular, widespread differences exist between regions and practice on the availability and use of intradermal testing (IDT) and patch testing, the standard drug concentrations used, the use of additional drugs in IDT and patch testing to help determine cross-reactivity, the timing of testing in relation to the occurrence of the adverse drug reaction, the use of testing in specific phenotypes, and the use of oral challenge in conjunction with delayed intradermal and patch testing to ascertain drug tolerance. It was noted that there have been advances in the science of delayed T-cell mediated reactions that have shed light on immunopathogenesis and provided a mechanism of pre-prescription screening in the case of HLA-B*57:01 and abacavir hypersensitivity and HLA-B*15:02 and carbamazepine SJS/TEN in Southeast Asians. Future directions should include the collaboration of large international networks to develop and standardize in vivo diagnostic approaches such as skin testing and patch testing combined with ex vivo and in vitro laboratory approaches.
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            Controversies in Drug Allergy: Drug Allergy Pathways

            Drug allergy pathways are standardized approaches for patients reporting prior drug allergies with the aim of quality improvement and promotion of antibiotic stewardship. At the International Drug Allergy Symposium during the 2018 American Academy of Allergy, Asthma and Immunology /World Allergy Organization Joint Congress in Orlando, Florida, drug allergy pathways were discussed from international perspectives with a focus on beta-lactam allergy pathways and pragmatic approaches for acute care hospitals. In this expert consensus document, we review current pathways, and detail important considerations in devising, implementing, and evaluating beta-lactam allergy pathways for hospitalized patients. We describe the key patient and institutional factors that must be considered in risk stratification, the central feature of pathway design. We detail shared obstacles to widespread beta-lactam allergy pathway implementation, and identify potential solutions to address these challenges.
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              Controversies in drug allergy: Beta-lactam hypersensitivity testing

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                Author and article information

                Contributors
                +1 858-573-5397 , michael.x.schatz@kp.org
                Journal
                World Allergy Organ J
                World Allergy Organ J
                The World Allergy Organization Journal
                BioMed Central (London )
                1939-4551
                19 December 2018
                19 December 2018
                2018
                : 11
                : 1
                : 41
                Affiliations
                [1 ]ISNI 0000 0004 0445 1191, GRID grid.414895.5, Department of Allergy, , Kaiser Permanente Medical Center, ; 7060 Clairemont Mesa Boulevard, San Diego, California 92111 USA
                [2 ]Hospital Bambino Gesù in Rome, Vatican City, Italy
                [3 ]ISNI 0000 0000 9259 8492, GRID grid.22937.3d, Medical University Vienna and Messerli Research Institute, ; Vienna, Austria
                [4 ]ISNI 0000 0004 1936 8294, GRID grid.214572.7, Univiersity of Iowa and the Iowa City VA, ; Iowa City, IA USA
                Article
                223
                10.1186/s40413-018-0223-2
                6299546
                e569a4b0-81b5-4a2b-8bfc-497382966236
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 1 November 2018
                : 8 November 2018
                Categories
                Editorial
                Custom metadata
                © The Author(s) 2018

                Immunology
                drug allergy,hypersensitivity,beta-lactam,radiographic contrast media,in vitro allergy testing,delayed drug reactions

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