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J Allergy Clin Immunol. 2019 Jan;143(1):66-73. doi: 10.1016/j.jaci.2018.10.030. Epub 2018 Dec 17.

Controversies in drug allergy: Testing for delayed reactions.

Author information

Vanderbilt University Medical Center, Nashville, Tenn; Institute for Immunology and Infectious Diseases, Murdoch, Australia. Electronic address:
Department of Dermatology, Dermato-Allergy Division, University of Minnesota, Minneapolis, Minn.
Department of Dermatology, Allergy Unit, University Hospital, University of Basel, Basel, Switzerland.
Boston Children's Hospital and Harvard Medical School, Boston, Mass.
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Linkou and Keelung, Taiwan.
Division of Dermatology and Combined Drug Allergy Clinic, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Department of Dermatology, Dokumentationszentrum schwerer Hautreaktionen (dZh), Medical Center and Medical Faculty, University of Freiburg, Freiburg, Germany.
Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.
Université Paris-Est Créteil, Créteil, France.
Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
University Hospital of Montpellier, Montpellier, and Sorbonne Université, INSERM, Paris, France; Hospital Sírio Libanês, São Paulo, Brazil.
Department of Infectious Diseases and Centre for Antibiotic Allergy and Research, Austin Health, University of Melbourne, Heidelberg, Australia; National Centre for Infections in Cancer, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Parkville, Australia.
Allergy Department, Pediatric Hospital Bambino Gesù, Rome, Vatican City, Italy.
Dermatology and Allergy Department, Tenon Hospital, Medecine Sorbonne University, Paris, France; Assistance publique-hopitaux de Paris, Paris, France.


Controversies exist with regard to in vivo approaches to delayed immunologically mediated adverse drug reactions, such as exanthem (maculopapular eruption), drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and fixed drug eruptions. In particular, widespread differences exist between regions and practice on the availability and use of intradermal and patch testing, the standard drug concentrations used, the use of additional drugs in intradermal 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 preprescription screening in the case of HLA-B*57:01 and abacavir hypersensitivity and HLA-B*15:02 and carbamazepine Stevens-Johnson syndrome/toxic epidermal necrolysis in Southeast Asian subjects. 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.


Delayed; HLA; Stevens-Johnson syndrome/toxic epidermal necrolysis; acute generalized exanthematous pustulosis; drug reaction with eosinophilia and systemic symptoms; fixed drug eruption; intradermal; oral challenge; patch; prick

[Available on 2020-01-01]
[Indexed for MEDLINE]

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