Optimizing the State of the Immune System, Diagnosis and Treatment in Children with a Background of Hypersensitivity to Drugs

Abstract

Drug use in children is–in most cases–supported by extrapolation of data generated from clinical trials in adult populations. This puts children at higher risk of developing adverse drug reactions (ADRs) due to “off-label” use of drugs and dosing issues. Major types of ADRs are drug hypersensitivity reactions, an idiosyncratic type of  ADRs that are largely unpredictable and can cause high morbidity and mortality in a hard-to-identify specific population of patients. Lack of a complete understanding of the pathophysiology of  DHRs and their unpredictive nature make them problematic in clinical practice and in drug development. In addition, ethical and legal obstacles hinder conducting large clinical trials in children, which in turn make children a “therapeutic orphan” where clear clinical guidelines are lacking, and practice is based largely on the personal experience of the clinician, hence making modeling desirable. This brief review summarizes the current knowledge of model-based evaluation of diagnosis and management of drug hypersensitivity reactions (DHRs) to antimicrobial drugs in the pediatric population. Ethical and legal aspects of drug research in children and the effect of different stages of child development and other factors on the risk of  DHRs are discussed