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      Drug Allergy in Children: What Should We Know?

      review-article
      , MD, , MD, PhD
      Clinical and Experimental Pediatrics
      Korean Pediatric Society
      Adverse drug reaction, Drug allergy, Drug hypersensitivity, Drug provocation test

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          Abstract

          The drug allergy “label” may have a lifetime of consequences for a child. Many children with alleged drug allergies are proven to be tolerant to the culprit medication when challenged. The field of drug hypersensitivity is a recently evolving field of research, but studies on its epidemiology and diagnostic tools are lacking in children. Clinical history is significant in the diagnosis and classification of drug hypersensitivity in children. Diagnostic tools have been evaluated in a limited number of children; therefore, the guidelines are mainly in line with those for adults. Here, we review the clinical characteristics, main drugs, risk factors, and diagnosis of drug hypersensitivity to aid in its accurate diagnosis in children.

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          Most cited references74

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          Drug allergy: an updated practice parameter.

          , , (2010)
          Adverse drug reactions (ADRs) result in major health problems in the United States in both the inpatient and outpatient setting. ADRs are broadly categorized into predictable (type A and unpredictable (type B) reactions. Predictable reactions are usually dose dependent, are related to the known pharmacologic actions of the drug, and occur in otherwise healthy individuals, They are estimated to comprise approximately 80% of all ADRs. Unpredictable are generally dose independent, are unrelated to the pharmacologic actions of the drug, and occur only in susceptible individuals. Unpredictable reactions are subdivided into drug intolerance, drug idiosyncrasy, drug allergy, and pseudoallergic reactions. Both type A and B reactions may be influenced by genetic predisposition of the patient
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            Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices—United States, 2018–19 Influenza Season

            Summary This report updates the 2017–18 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2017;66[No. RR-2]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. A licensed, recommended, and age-appropriate vaccine should be used. Inactivated influenza vaccines (IIVs), recombinant influenza vaccine (RIV), and live attenuated influenza vaccine (LAIV) are expected to be available for the 2018–19 season. Standard-dose, unadjuvanted, inactivated influenza vaccines will be available in quadrivalent (IIV4) and trivalent (IIV3) formulations. Recombinant influenza vaccine (RIV4) and live attenuated influenza vaccine (LAIV4) will be available in quadrivalent formulations. High-dose inactivated influenza vaccine (HD-IIV3) and adjuvanted inactivated influenza vaccine (aIIV3) will be available in trivalent formulations. Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 25, 2017; February 21, 2018; and June 20, 2018. New and updated information in this report includes the following four items. First, vaccine viruses included in the 2018–19 U.S. trivalent influenza vaccines will be an A/Michigan/45/2015 (H1N1)pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent influenza vaccines will contain these three viruses and an additional influenza B vaccine virus, a B/Phuket/3073/2013–like virus (Yamagata lineage). Second, recommendations for the use of LAIV4 (FluMist Quadrivalent) have been updated. Following two seasons (2016–17 and 2017–18) during which ACIP recommended that LAIV4 not be used, for the 2018–19 season, vaccination providers may choose to administer any licensed, age-appropriate influenza vaccine (IIV, RIV4, or LAIV4). LAIV4 is an option for those for whom it is appropriate. Third, persons with a history of egg allergy of any severity may receive any licensed, recommended, and age-appropriate influenza vaccine (IIV, RIV4, or LAIV4). Additional recommendations concerning vaccination of egg-allergic persons are discussed. Finally, information on recent licensures and labeling changes is discussed, including expansion of the age indication for Afluria Quadrivalent (IIV4) from ≥18 years to ≥5 years and expansion of the age indication for Fluarix Quadrivalent (IIV4), previously licensed for ≥3 years, to ≥6 months. This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2018–19 season in the United States. A Background Document containing further information and a brief summary of these recommendations are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used within Food and Drug Administration–licensed indications. Updates and other information are available at CDC’s influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check CDC’s influenza website periodically for additional information.
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              The lymphocyte transformation test in the diagnosis of drug hypersensitivity.

              Diagnosis of drug hypersensitivity is difficult, as an enormous amount of different drugs can elicit various immune-mediated diseases with distinct pathomechanism. The lymphocyte transformation test (LTT) measures the proliferation of T cells to a drug in vitro--from which one concludes to a previous in vivo reaction due to a sensitization. This concept of the LTT has been confirmed by the generation of drug-specific T-cell clones and the finding that drugs can directly interact with the T-cell receptor, without previous metabolism or need to bind to proteins. In this review, technical aspects and usefulness of this test for the diagnosis of drug hypersensitivity are discussed. The main advantage of this test is its applicability with many different drugs in different immune reactions, as drug-specific T cell are almost always involved in drug hypersensitivity reactions. Its main disadvantages are that an in vitro proliferation of T cells to a drug is difficult to transfer to the clinical situation and that the test per se is rather cumbersome and technically demanding. In addition, its sensitivity is limited (for beta-lactam allergy it is in the range of 60-70%), - although at least in our hands - it is higher than of other tests for drug hypersensitivity diagnosis. Consequently, drug hypersensitivity diagnosis needs to rely on a combination of history and different tests, as none of the single tests available has per se a sufficiently good sensitivity. Within this setting, the LTT has proven to be a useful test for the diagnosis of drug hypersensitivity reactions and helped to better understand these reactions. Further work on the simplification of this test and systematic evaluation of its sensitivity and specificity in some main groups of drugs are necessary to make this test more widely available.
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                Author and article information

                Journal
                Clin Exp Pediatr
                Clin Exp Pediatr
                CEP
                Clinical and Experimental Pediatrics
                Korean Pediatric Society
                2713-4148
                June 2020
                12 November 2019
                : 63
                : 6
                : 203-210
                Affiliations
                Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
                Author notes
                Corresponding author: Dong In Suh, MD, PhD. Department of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul 03080, Korea E-mail: dongins0@ 123456snu.ac.kr
                Author information
                http://orcid.org/0000-0002-7817-8728
                Article
                kjp-2019-00675
                10.3345/kjp.2019.00675
                7303428
                32024327
                a2a3103c-9300-4621-9f3b-de6e9931c926
                Copyright © 2020 by The Korean Pediatric Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 June 2019
                : 8 November 2019
                : 12 November 2019
                Categories
                Review Article
                Allergy

                adverse drug reaction,drug allergy,drug hypersensitivity,drug provocation test

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