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      Important questions in drug allergy and hypersensitivity: consensus papers from the 2018 AAAAI/WAO international drug allergy symposium

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          Abstract

          This article is one of a series of international consensus documents developed from the International Drug Allergy Symposium held at the Joint Congress of the American Academy of Allergy, Asthma & Immunology/World Allergy Organization on March 1, 2018, in Orlando, Florida, USA. The symposium was sponsored by The Journal of Allergy and Clinical Immunology, The Journal of Allergy and Clinical Immunology: In Practice, and The World Allergy Organization Journal and chaired by Mariana Castells, MD, PhD, and Pascal Demoly, MD, PhD.

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          Most cited references 7

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          Self-reported drug allergy in a general adult Portuguese population.

          To estimate the prevalence of self-reported drug allergy in adults. Cross-sectional survey of a general adult population from Porto (all of whom were living with children involved in the International Study of Asthma and Allergies in Childhood-phase three), during the year 2002, using a self-administered questionnaire. The prevalence of self-reported drug allergy was 7.8% (181/2309): 4.5% to penicillins or other beta-lactams, 1.9% to aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and 1.5% to other drugs. In the group 'allergic to beta-lactams', the most frequently implicated drug was penicillin G or V (76.2%) followed by the association of amoxicillin and clavulanic acids (14.3%). In the group 'allergic to NSAIDs', acetylsalicylic acid (18.2%) and ibuprofen (18.2%) were the most frequently identified drugs, followed by nimesulide and meloxicam. Identification of the exact name of the involved drug was possible in less than one-third of the patients, more often within the NSAID group (59.5%). Women were significantly more likely to claim a drug allergy than men (10.2% vs. 5.3%). The most common manifestations were cutaneous (63.5%), followed by cardiovascular symptoms (35.9%). Most of the reactions were immediate, occurring on the first day of treatment (78.5%). Only half of the patients were submitted to drug allergy investigations. The majority (86.8%) completely avoided the suspected culprit drug thereafter. The results showed that self-reported allergy to drugs is highly prevalent and poorly explored. Women seem to be more susceptible. beta-lactams and NSAIDs are the most frequently concerned drugs.
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            Drug provocation tests in patients with a history suggesting an immediate drug hypersensitivity reaction.

            Drug hypersensitivity reactions are common and can be life-threatening. Confirmation of the diagnosis should be rigorous and based on clinical history and a physical examination, possibly followed by skin tests and drug provocation tests. To describe the outcome of drug provocation tests in evaluating patients with histories suggesting drug allergy. Retrospective analysis of clinic case series. The department for drug allergy at a university hospital. 898 consecutive patients with suspected immediate drug allergy referred to the clinic between September 1996 and August 2001. Patients with severe skin reactions and those with positive results on skin tests for beta-lactams were excluded. Single-blinded administration of increasing doses of the suspected drug, up to the usual daily dose, under strict hospital surveillance. 1372 drug provocation tests were performed using various drugs, including beta-lactams (30.3%), aspirin (14.5%), other nonsteroidal anti-inflammatory drugs (11.7%), paracetamol (8.9%), macrolides (7.4%), and quinolones (2.4%). There were 241 (17.6%) positive drug provocation test results. Drug provocation reproduced the same symptoms, albeit milder and of a shorter duration, in the following patients: 13 (5.4%) with a history of anaphylactic shock, 17 (7.0%) with a history of anaphylaxis without shock, 10 (4.1%) with a history of laryngeal edema, 19 (7.9%) with a history of bronchospasm, 160 (66.4%) with a history of urticaria, and 22 (9.1%) with a history of maculopapular eruption. All adverse reactions were completely reversed by prednisolone, H(1)-antihistamines, and epinephrine as needed. Falsely negative results on drug provocation tests may have occurred because of loss of sensitization, rare cofactors not included in the diagnostic procedure, and tolerance induction during provocation. Drug provocation tests in individuals with suspected drug allergy performed in carefully controlled settings can confirm drug hypersensitivity.
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              Approach to the diagnosis of drug hypersensitivity reactions: similarities and differences between Europe and North America

              Drug hypersensitivity reactions (DHRs) affect an unknown proportion of the general population, and are an important public health problem due to their potential to cause life-threatening anaphylaxis and rare severe cutaneous allergic reactions. DHR evaluations are frequently needed in both ambulatory and hospital settings and have a complex diagnosis that requires a detailed clinical history and other tests that may include in vitro tests and in vivo procedures such as skin tests and drug provocation tests. Although over the years both European and U.S. experts have published statements on general procedures for evaluating DHRs, a substantial discordance in their daily management exists. In this review, we highlight both the differences and the similarities between the European and U.S. perspectives. While a general consensus exists on the importance of skin tests for evaluating DHRs, concordance between Americans and Europeans exists solely regarding their use in immediate reactions and the fact that a confirmation of a presumptive diagnosis by drug provocation tests is often the only reliable way to establish a diagnosis. Finally, great heterogeneity exists in the application of in vitro tests, which require further study to be well validated.
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                Author and article information

                Contributors
                pascal.demoly@inserm.fr
                mcastells@partners.org , mcastells@bwh.harvard.edu
                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
                Affiliations
                [1 ]ISNI 0000 0001 2308 1657, GRID grid.462844.8, Department of Pulmonology, Division of Allergy, , Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Univ Montpellier and Equipe EPAR, IPLESP, INSERM Sorbonne Université, ; Paris, France
                [2 ]Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, 60 Fenwood Road, Room 5002N Hale BTM Building, Boston, MA 02115 USA
                [3 ]Drug Hypersensitivity and Desensitizations Center, Brigham and Women’s Hospital, Harvard Medical School, 60 Fenwood Road, Room 5002N Hale BTM Building, Boston, MA 02115 USA
                [4 ]ISNI 000000041936754X, GRID grid.38142.3c, Mastocytosis Center, Brigham and Women’s Hospital, , Harvard Medical School, ; 60 Fenwood Road, Room 5002N Hale BTM Building, Boston, MA 02115 USA
                Article
                224
                10.1186/s40413-018-0224-1
                6299668
                © 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.

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