Nomenclature on Immune‐Mediated Drug Reactions: An EAACI Position Paper

Abstract

Over the past several decades, there have been significant advances in our understanding of both immunological and pharmacological mechanisms of adverse drug reactions (ADRs). Immune‐mediated drug reactions (IMDRs) represent a small proportion of ADRs and are caused by a pathological activation of the immune system or inflammatory pathways. Drugs can act as an antigen or may directly interact with the immune system or inflammatory pathways, making immune‐mediated drug reactions observed in contemporary practice not sufficiently explained by the Gell and Coombs (G&C) framework. Moreover, the phenotype alone is neither pathognomonic nor sufficient to infer the endotype. The proposed nomenclature integrates chrono‐morphological phenotypes, mechanistic endotypes and characteristics of the involved drug. In this nomenclature, IMDRs are classified, according to the nature of interaction with the immune system, in: (i) drug allergy that encompasses antigen‐driven reactions—diagnosed by tests detecting sensitisation—and (ii) drug hypersensitivity that includes the heterogeneous broad group of drug‐directly‐driven reactions. This framework supports precision medicine, aligns terminology with mechanisms, and provides a common language for interdisciplinary communication, pharmacovigilance, and drug development. It accommodates emerging therapeutic classes and remains adaptable to future discoveries in immunopathogenesis and biomarker development.