Hypersensitivity adverse drug reactions in children: Pathophysiology and therapeutic implications

Background: Adverse drug reactions are common problems for children and adults. Among the most serious are hypersensitivity reactions. The pathogenesis of these reactions has not been understood, but recently there have been new insights into the mechanism(s) responsible for these complex adverse drug reactions. Objectives: The goals of this paper were to review potential mechanisms for hypersensitivity adverse drug reactions and to relate these mechanisms to the care of children with hypersensitivity reactions. Methods: A search for original research in the pathogenesis of hypersensitivity adverse drug reactions was done using MEDLINE from 1985 to 2001. Other databases were not consulted. The research reviewed was confined to that described in English. Results: Hypersensitivity adverse drug reactions appear to be initiated by metabolism of the parent drug to reactive intermediates. The ongoing propagation of these reactions appears to be mediated by immunity. The mechanism(s) involved in the immunopathogenesis of drug hypersensitivity reactions mediated by reactive drug metabolites remains unclear, but may include changes in T-cell responses mediated by changes in T-cell signaling. Conclusions: Hypersensitivity adverse drug reactions are important challenges for health care workers caring for children. Health care workers need to be vigilant for the development of hypersensitivity adverse drug reactions and be aware that these reactions may continue to evolve clinically despite discontinuation of the drug in question.