The Journal of Allergy and Clinical Immunology: In Practice
Clinical Commentary ReviewAdvances in the Understanding of Drug Hypersensitivity: 2012 Through 2022
Section snippets
Epidemiology
Looking at what really happens in large populations is essential to the understanding of the risks and benefits of promoting of safe drug use through appropriate labeling of true and life-threatening drug hypersensitivity and delabeling low-risk and unverified drug “allergy” labels. One of the most impactful advances in the understanding of drug hypersensitivity in the past decade has been the development and mining of integrated EHRs that contain all outpatient, inpatient, and pharmacy records
Mechanisms of Drug Hypersensitivity
Over the last decade our understanding of the pathogenesis of adverse drug reactions including drug hypersensitivity reactions (DHR) has evolved along with advances in our understanding of their cellular and molecular basis. The Gell-Coombs classification of immune-mediated drug reactions remains relevant, with type I (IgE mediated) and type IV (T-cell mediated) still being the most commonly confirmed in clinical practice.49 However, recent evolution in the understanding of the
Diagnostic Procedures
Diagnostic tests remain a key part of the investigation and understanding of DHR.13,79 However, recent guidelines from the American Academy of Allergy Asthma and Immunology and the European Association of Allergy and Clinical Immunology/European Network of Drug Allergy on diagnostic drug allergy workup specifically include pragmatic alternative pathways, under conditions of imminent drug need or when the pretest probability is low, using minimal diagnostic procedures and more reliance on direct
Practical Interventions
Rechallenge with the implicated and/or structurally related drugs can cause a life-threatening recurrence in SCARs, and these are classical contraindications of a drug challenge.13 Drug challenges when a serious T-cell–mediated mechanism is suspected should not be attempted in the presence of effective alternative drugs.13 Exceptions exist in low- and middle-income countries where diseases of high global burden, such as HIV and tuberculosis, demand complex treatment regimens with no affordable
Conclusions
The last decade, from 2012 to 2022, has represented a period of significant achievement in the field of drug hypersensitivity. Some of the key advances are delineated in Table I. For immunologically mediated adverse drug reactions, advances in knowledge of mechanisms and genetic discoveries have informed individual risk assessment and are leading to implementation strategies to facilitate prevention, earlier and more precise diagnosis, and targeted management strategies. History and allergy
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No funding was received for this work.
Conflicts of interest: A. M. Chiriac is a member of the Advisory Board for Drug Allergy for HYCOR. She has received lecture fees from ThermoFisher Scientific. P. Demoly reports no conflicts of interest for this paper. He has received board fees via his department from Stallergenes Greer, ALK, AstraZeneca, Menarini, Sanofi, Viatris, Puressentiels, GSK, Novartis, and Zambon. E. J. Phillips has received grants and funding from the National Institutes of Health (R01HG010863, R01AI152183, U01AI154659, R13AR078623, UAI109565), royalties from UpToDate, and consulting fees from Janssen, Vertex, Biocryst, Regeneron, Verve, and AstraZeneca. She is co-director of IIID Pty Ltd, which holds a patent for HLA-B 5701 testing for abacavir hypersensitivity and a patent pending for detection of HLA-A 32:01 in connection with diagnosing DRESS, without any financial remuneration and not directly related to the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.