Controversies in drug allergy: Testing for delayed reactions

Elizabeth J. Phillips, Paul Bigliardi, Andreas J. Bircher, Ana Broyles, Yoon Seok Chang, Wen Hung Chung, Rannakoe Lehloenya, Maja Mockenhaupt, Jonny Peter, Munir Pirmohamed, Jean Claude Roujeau, Neil H. Shear, Luciana Kase Tanno, Jason Trubiano, Rocco Valluzzi, Annick Barbaud

Research output: Contribution to journalReview articlepeer-review

146 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)66-73
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Issue number1
StatePublished - Jan 2019

Bibliographical note

Funding Information:
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.

Funding Information:
Disclosure of potential conflict of interest: E. J. Phillips receives funding from the National Institute of Health (NIH; GM115305-01, AI110527-01A1, AI139021, and AI136815) and the National Health and Research Council of Australia, royalties from UpToDate, and consultancy fees from Biocryst and is codirector of IIId Pty Ltd, which holds a patent for HLA-B*57:01 testing for abacavir hypersensitivity. A. J. Bircher receives royalties from UpToDate and consulting fees from VIFOR Pharma. M. Pirmohamed acknowledges funding from UK MRC (Centre for Drug Safety Science) and UK NIHR (NW Coast CLAHRC). J. Peter receives funding from the NIH (1K43TW011178-01). N. H. Shear is a consultant for Amgen, Abbvie, Celgene, Janssen, Leo Pharma, Lilly Canada, Novartis, and Sanofi Genzyme and receives royalties from Litt's Drug Rruption and Reaction Manual and Advances in Diagnosis and Management of Cutaneous Adverse Drug Reactions (Springer Nature). J. Trubiano receives funding from the National Health and Research Council of Australia. The rest of the authors declare that they have no relevant conflicts of interest.

Publisher Copyright:
© 2018 American Academy of Allergy, Asthma & Immunology


  • 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


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