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Clinical features prompting urgent (re)evaluation of amoxicillin-associated reactions in children

Published: July 21, 2022

Penicillin de-labeling efforts have gained tremendous momentum over the last 10 years, focusing on the safety and importance of provocation challenges in hospital or allergy office settings. Pediatric allergist Kimberly Risma, MD, PhD identified a critical barrier in de-labeling—incomplete recognition by allergists of the index reactions experienced by children taking penicillins. Therefore, Risma assembled a research team of pediatric residents and a pediatric emergency room specialist to carefully characterize the symptoms that prompt urgent evaluation of children with amoxicillin-associated reactions (AAR) in urgent care and emergency room settings.

Guarnieri et al. report the details of AAR presentations, including symptoms that prompt urgent evaluation, timing during the antibiotic course, and broader contextual factors, such as season of presentation, in The Journal of Allergy and Clinical Immunology: In Practice. The acute care cohort differed from previously described allergy referral populations, with a larger proportion of children with higher rates of systemic symptoms like fever, joint pain or swelling, frequently labeled as serum sickness-like reactions (SSLR). There was substantial overlap between those with hives and SSLRs during the winter respiratory viral season, whereas non-hive rashes occurred more frequently in the late spring or summer months, providing potential clues to differing underlying causes. Additionally, the bulk of all AARs started at days 7-10 of antibiotic courses, irrespective of rash type or presence of systemic symptoms.

Although Guarnieri et al.’s paper provides the groundwork for enhancing allergists’ clinical pattern recognition and diagnostic acumen to guide subsequent drug allergy evaluations, the most striking finding was that children presenting with AARs had an extraordinarily high acute care reutilization rate, with 10% of our cohort returning to the emergency or urgent care setting due to persistent and/or emerging symptoms. These findings prompted a further study by the same team, reported by Xie et al. in The Journal of Allergy and Clinical Immunology: In Practice, which identified that specific patients with AAR (i.e., toddlers with persistent hives) constituted the bulk of this re-utilization; up to 40% of these young patients returned for repeat evaluation. The team also identified potential gaps in counseling that they theorize may drive reutilization.

These studies support the assertion that AARs presenting to acute care settings differ in phenotypic composition from allergy referral populations and among clinical phenotypes, providing a foundation for future studies on risk stratification and rechallenge tolerance rates. Furthermore, counseling families during episodes of AAR may be a strategic intervention; for example, the allergy team at Cincinnati Children’s has initiated a telemedicine program dedicated to real-time evaluation of children who are experiencing AARs (referred by primary care and/or emergency room providers) to prevent costly and time-consuming acute care reutilization.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

Full Articles:
Predictors of acute care reutilization in pediatric patients with amoxicillin-associated reactions

Distinct characteristics and chronology of amoxicillin-associated reactions in pediatric acute care settings