Drug hypersensitivity reactions in children in clinical practice: A WAO Statement

Abstract

Drug hypersensitivity reactions (DHRs) in children and adolescents are less common than in adults but can have serious consequences if mismanaged. Mislabeling children as drug-allergic due to incomplete diagnostic evaluations leads to unnecessary medication restrictions, increased healthcare costs, and suboptimal treatment choices. This Statement from the World Allergy Organization (WAO) provides evidence-based recommendations for evaluating and managing pediatric DHRs, emphasizing accurate diagnosis through in vivo and in vitro testing, risk stratification, and personalized approaches. Antibiotics, particularly β-lactams, and non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently implicated drugs, with non-immediate reactions, such as maculopapular exanthema, being the most common presentation. The document also addresses emerging concerns, including monoclonal antibody-induced anaphylaxis and drug-induced enterocolitis syndrome. It underscores the need for specialized care in allergy centers with expertise in pediatric populations and advocates for multidisciplinary programs to manage complex cases, such as chemotherapy hypersensitivity and perioperative drug allergy. By addressing diagnostic challenges and clinical uncertainties, this document aims to improve the management of DHRs in children, reduce mislabeling, and enhance patient outcomes worldwide.

Fig. 1

Algorithmic Approach to Pediatric Drug Hypersensitivity Reactions (DHRs) to Chemotherapy and Biologics. ∗High-risk: The definition of high-risk should be local and incorporate factors beyond the severity of the index reaction, as per WAO guidance. A recent publication is an excellent example of how to apply risk assessment locally. Note on intensive care: As groups gain experience or expand capacity, they may eventually transition all procedures from intensive or semi-intensive care to an allergy-led technical area. Local adaptation is essential, including considerations for safe handling of hazardous drugs. A dotted line represents “selected cases”; IL-6, interleukin 6; RA, risk assessment; SCARs, severe cutaneous adverse reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson's Syndrome (SJS), or toxic epidermal necrolysis (TEN); SOPs, standard operating procedures

Fig. 2

Integrated Allergy Care Pathways for Pediatric Cystic Fibrosis Patients: A Comprehensive Approach to Patient-Centered Management. Note: Allergy champions are healthcare professionals who, regardless of their role or speciality, actively engage in coordinating and promoting allergy care within their respective areas. They serve as points of contact and liaise with the allergy team to ensure effective, safe, and patient-centered management. CF, cystic fibrosis; DHR, drug hypersensitivity reaction; DR T-cell clones, drug-responsive T-cell clones; IDT, intradermal testing; MDM, multidisciplinary meeting; RDD, rapid drug desensitization; SPT, skin prick testing.