Genetic markers of drug hypersensitivity in pediatrics: current state and promise

ABSTRACT

Introduction

Drug hypersensitivity reactions (DHRs) represent a great challenge to clinicians due to their unpredictability and severity, notably being potentially fatal. Genetic markers for DHRs have been emerging as potential valuable clinical tools for prediction and diagnosis of DHRs. Dedicated pediatric studies in this field are scarce and many published studies lack key data in this regard.

Area covered

This review briefly covers the current status of the use and validation of genetic markers for drug hypersensitivity in pediatrics. Classification, epidemiology and pathophysiology of DHRs are also briefly described. We searched PubMed, Ovid Medline, Web of Science, Scopus and Google Scholar literature databases for all relevant articles published from their date of commencement to March 2022. We summarized the current existing evidence and discussed the role and potential of pharmacogenomic testing in management of DHRs in pediatrics.

Expert opinion

Several genetic markers for DHRs in children have been identified and proven to be useful tools for prediction, diagnosis, and management of these adverse reactions. However, data in pediatric populations is still limited and confined to specific drugs in specific ethnic groups. Further research is needed to identify and validate more genetic markers to help guide drug therapy in children.

KEYWORDS:

• adverse drug reactions
• drug hypersensitivity
• drug allergy
• human leukocyte antigen
• pediatric
• children. CYP450
• pharmacogenomics
• pharmacogenetics

Article highlights

• Drug hypersensitivity reactions (DHRs) are difficult to predict or diagnosis as being unrelated to the drug’s known pharmacology and being dose independent.

• Pediatric patients seem to be at higher risk of developing DHRs to specific classes of drugs including antibiotics, antiepileptics and NSAIDs.

• The pathophysiology of DHRs is not well understood but evidence support their being immune mediated.

• Labelling a child as ‘drug allergic’ can have dire consequences to their health and significantly increase healthcare cost.

• Several genetic markers have been identified and validated for DHRs but this is only limited to certain drugs.

• Much research work is needed to expand the field of pharmacogenomics to optimize drug therapy in children.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.