Nonimmediate drug hypersensitivity reactions (NI-DHR) constitute the most complex group of drug allergy, with many drugs involved. Both parent drugs and their reactive metabolites can be implicated. Although with some drugs the number of metabolites is limited, with others it is quite extensive and many still remain to be identified. The diagnostic approaches are insufficient for the diagnosis and realistic approaches that reproduce the pathological response are lacking.
A wider view has now been considered, with the inclusion of several mechanisms that may contribute to drug hypersensitivity reactions (DHR): the classical hapten hypothesis, the danger signal and the pharmacological interaction. Monitoring the acute response provides relevant information about the mechanisms involved, with the identification of a large number of genes that can be over-expressed or under-expressed in the acute phase of the response. Assessment of risk of developing reactions can be verified by HLA associations.
Further knowledge of these NI-DHR, including molecular genetics and transcriptomic analysis, has enabled a better understanding and management of these reactions.
aRoche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland
bGeneral University Hospital of Alicante
cInfanta Leonor University Hospital, Allergy Service, Madrid, Spain
Correspondence to E. Gómez, Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Brunngasse, 40. 4153. Reinach. BL., Switzerland. Tel: +41 76 321 40 37; e-mail: firstname.lastname@example.org