The role of penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge

J Allergy Clin Immunol. 2011 Jan;127(1):218-22. doi: 10.1016/j.jaci.2010.08.025. Epub 2010 Oct 28.


Background: Delayed-onset urticarial or maculopapular rashes are frequently observed in children treated with β-lactams. Many are labeled "allergic" without reliable testing.

Objective: Determine the etiology of these rashes by exploring both infectious and allergic causes.

Methods: Children presenting to the emergency department with delayed-onset urticarial or maculopapular rashes were enrolled. Acute and convalescent sera were obtained for viral screening along with a throat swab. Subjects underwent intradermal and patch skin testing for β-lactams 2 months after presentation. Anti-β-lactam blood allergy tests were also obtained. All subjects underwent an oral challenge test (OCT) with the culprit antibiotic.

Results: Eighty-eight children were enrolled between 2006 and 2008. There were 11 (12.5%) positive intradermal and no positive patch tests. There were 2 (2.3%) positive blood allergy tests. There were 6 (6.8%) subjects with a positive OCT, 2 were intradermal-negative, and 4 were intradermal-positive. No OCT reactions were more severe than the index event. Most subjects had at least 1 positive viral study, 54 (65.9%) in the OCT negative group.

Conclusion: In this situation, β-lactam allergy is clearly overdiagnosed because the skin rash is only rarely reproducible (6.8%) by a subsequent challenge. Viral infections may be an important factor in many of these rashes. OCTs were positive in a minority of intradermal skin test-positive subjects. Patch testing and blood allergy testing provided no useful information. OCTs should be considered in all children who develop a delayed-onset urticarial or maculopapular rash during treatment with a β-lactam.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / adverse effects*
  • Child
  • Child, Preschool
  • Drug Eruptions / diagnosis
  • Drug Eruptions / epidemiology
  • Drug Eruptions / etiology*
  • Exanthema / diagnosis
  • Exanthema / etiology*
  • Female
  • Humans
  • Infant
  • Male
  • Penicillins / adverse effects*
  • Skin Tests


  • Anti-Bacterial Agents
  • Penicillins