Novel insights into molecular and cellular aspects of delayed drug hypersensitivity reactions

Delayed drug hypersensitivity reactions (DDHRs) represent a major health problem. They are unpredictable and can cause life-long disability or even death. The pathophysiology of DDHRs is complicated, multifactorial, and not well understood mainly due to the lack of validated animal models or in vitro systems. The role of the immune system is well demonstrated but its exact pathophysiology still a matter of debate.

This review summarizes the current understanding of DDHRs pathophysiology and abridges the available new evidence supporting each hypothesis. A comprehensive literature search for relevant publications was performed using PubMed, Google Scholar, and Medline databases with no date restrictions and focusing on the most recent 10 years.

Although multiple milestones have been achieved in our understanding of DDHRs pathophysiology as a result of the development of useful experimental models, many questions are yet to be fully answered. A deeper understanding of the mechanistic basis of DDHRs would not only facilitate the development of robust and reliable diagnostic assays for diagnosis, but would also inform therapy by providing specific target(s) for immunomodulation and potentially permit pre-therapeutic risk assessment to pursue the common goal of safe and effective drug therapy.