Differentiating Between β-Lactam-Induced Serum Sickness-Like Reactions and Viral Exanthem in Children Using a Graded Oral Challenge

Luca Delli Colli, Sofianne Gabrielli, Elissa M Abrams, Andrew O'Keefe, Jennifer L P Protudjer, Elana Lavine, Tracy Pitt, Adelle Atkinson, Thomas Eiwegger, Christine McCusker, Moshe Ben-Shoshan

Research output: Journal article (peer-reviewed)Journal article

19 Citations (Scopus)


BACKGROUND: Serum sickness-like reactions (SSLRs) are defined by the presence of rash (primarily urticaria) and joint complaints (arthralgia/arthritis) that are believed to occur due to a non-IgE-mediated response to medications. However, similar reactions can occur due to viral infections, and it can be difficult to distinguish between the two. This may lead to unnecessary avoidance of the culprit antibiotic.

OBJECTIVE: We aimed to evaluate children presenting with suspected SSLRs through a graded oral challenge (GOC).

METHODS: All children referred to the Montreal Children's Hospital for potential antibiotic allergy (β-lactam or other antibiotics) and a clinical presentation compatible with SSLR were recruited for the study between March 2013 and February 2020. A standardized survey with questions on treatment, symptoms, and associated factors was completed, and a GOC (10% and subsequently 90% of the oral antibiotic dose) was conducted. Patients with a negative GOC were contacted annually to query on subsequent antibiotic use.

RESULTS: Among 75 patients presenting with suspected SSLRs, the median age was 2.0 years and 46.7% were males. Most reactions were attributed to amoxicillin. Among the 75 patients, 2.7% reacted immediately (within 1 hour) to a GOC and 4.0% had a nonimmediate reaction. Of the 43 patients successfully contacted, 20 reported subsequent culprit antibiotic use of whom 25.0% had a subsequent mild reaction (macular/papular rash).

CONCLUSIONS: This is the first and largest pediatric study to assess SSLR using a GOC. Our findings suggest that using a GOC is safe and appropriate for differentiating between β-lactam-induced SSLR and viral exanthem in this population.

Original languageEnglish
Pages (from-to)916-921
Number of pages6
JournalJournal of Allergy and Clinical Immunology: In Practice
Issue number2
Publication statusPublished - Feb 2021
Externally publishedYes


  • Amoxicillin/adverse effects
  • Anti-Bacterial Agents/adverse effects
  • Child
  • Child, Preschool
  • Drug Hypersensitivity/diagnosis
  • Exanthema/diagnosis
  • Female
  • Humans
  • Male
  • Serum Sickness
  • Skin Tests
  • Virus Diseases/diagnosis
  • beta-Lactams/adverse effects


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