With regard to the classification used in the article (1), it should be added that adverse drug reactions (ADRs) are increasingly no longer classified as type A and type B reactions (this classification originates from 1977 ), but rather as off-target and on-target reactions (3). The decision criterion here is whether or not an ADR is related to the pharmacological effect of a drug at its target site. Broadly speaking, off-target reactions (such as certain infusion reactions to biologics) correspond in a broader sense to type B reactions, whereas type A reactions are a kind of on-target reaction. The background to this is that also type A reactions may depend on individual genetic factors, and certain type B reactions can also be dose-dependent and predictable (3).
Regarding the pathophysiology of non-allergic hypersensitivity reactions, a 2015 Nature paper described a mast cell receptor in both a mouse model and human mast cells, which could be responsible for the IgE-independent release of histamine from mast cells (for instance, due to neuromuscular blocking agents, such as atracurium) (4).
Contrary to an adverse event, the definition of an ADR is based on the suspected causal relationship with the use of a medicinal product (§4  German Medicines Act, and §3  GCP Regulation). For example, an accidental leg fracture may constitute an adverse event that occurs when using a medicinal product without necessarily being causally related to the use of the medicinal product.
Prof. Dr. med. Bernhardt Sachs
Bundesinstitut für Arzneimittel und Medizinprodukte
Abteilung Forschung, Bonn, Germany
|1.||Böhm R, Proksch E, Schwarz T, Cascorbi I: Drug hypersensitivity—diagnosis, genetics, and prevention. Dtsch Arztebl Int 2018; 115: 501–1 VOLLTEXT|
|2.||Rawlins MD, Thompson JW: Pathogenesis of adverse drug reactions. In: Davies DM, eds.: Textbook of adverse drug reactions. Oxford, Oxford University Press 1977; 10–17.|
|3.||Garon SL, Pavlos RK, White KD, Brown NJ, Stone CA Jr, Phillips EJ: Pharmacogenomics of off-target adverse drug reactions. Br J Clin Pharmacol 2017; 83: 1896–1911 CrossRef MEDLINE PubMed Central|
|4.||McNeil BD, Pundir P, Meeker S, et al.: Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature 2015. 519: 237–41 CrossRef MEDLINE PubMed Central|