Recent developments in drug hypersensitivity in children

ABSTRACT

Introduction: Drug allergy is an important public health problem that causes 0.4–10.3% of hospital admissions in children. The epidemiology, clinical spectrum, diagnosis, and management of drug hypersensitivity reactions (DHRs) differ in pediatric and adult patients. However, the same algorithms used in adults have often been applied in the pediatric population due to a lack of evidence in the literature.

Areas covered: In this review, we aimed to discuss recent developments in the area of pediatric DHRs based on the growing body of literature advancing our understanding of the epidemiology, clinical aspects, and diagnostic approaches to DHRs in children.

Expert opinion: Misdiagnosis, under-diagnosis, and self-diagnosis are common problems related to drug allergies in children. Viral infections are particularly frequent in children and make diagnosis difficult. Identifying true DHR is a key step in the management of drug allergy in children. Therefore, a complete allergy work-up with standardized drug allergy tests is necessary. In order to eliminate non-standardized tests, future studies including larger numbers of children should be conducted to determine more accurate standardized tests for diagnosing DHRs in the pediatric population.

KEYWORDS:

• Children
• drug hypersensitivity
• drug allergy
• management
• recent developments

Article Highlights

• The most common causes of DHRs in the pediatric population are beta-lactam (BL) antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and non-BL antibiotics.

• Skin tests performed with classic penicillin and any suspect BL components are important to identify cross-reactivity among BLs.

• The diagnostic approach to suspected nonimmediate hypersensitivity has changed over the last decade. Skin tests (delayed-reading intradermal test and patch tests) and lymphocyte transformation tests followed by a DPT in case of negative skin tests was described previously. However, skin tests are not suitable for diagnosing nonimmediate mild cutaneous reactions associated with BL antibiotics in children. DPT can be performed for children with nonimmediate mild cutaneous reactions without previous skin tests.

• DHRs to nonsteroidal anti-inflammatory drugs (NSAIDs) are classified as selective allergic reactions (SR) (usually due to an immunological mechanism to a single or single subclass of NSAID) and nonallergic cross-intolerance (CI) reactions (related to the COX-1 inhibition and decrease in prostaglandin-E2 synthesis). However, 40% of confirmed NSAID hypersensitivity in children cannot be classified according to EAACI/ENDA suggestions. Further research is needed to better define and categorize DHRs to NSAIDs in different age groups.

• Antipyretic doses of paracetamol (weak COX-I/II inhibitor) can be tolerated by most children with CI to NSAIDs. Additionally, COX-II inhibitors including nimesulide, meloxicam, tolmetin, and etoricoxib may be safe for these patients. However, COX-II-specific inhibitors are not approved for general usage in children under 12 years of age.

• Antiepileptic drugs (AEDs) can lead to hypersensitivity reactions during childhood, but less frequently than with antibiotics and NSAIDs. AEDs are important because they are the leading cause of severe cutaneous adverse reactions, especially aromatic AEDs.

• Younger age, concomitant medications, high initial dose, rapid dose escalation, and certain genetic markers (metabolic enzyme mutations and some HLA genotypes) are significant risk factors for AED-related hypersensitivity. Viral infections (especially HHV) can also play a role in DHRs to AEDs.

• Genetic polymorphisms in HLA genes have recently been described as a powerful tool in the prediction of adverse reactions to some AEDs, especially CBZ.

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.