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J Allergy Clin Immunol Pract. 2015 May-Jun;3(3):375-80.e1. doi: 10.1016/j.jaip.2014.11.001. Epub 2015 Jan 16.

Amoxicillin allergy in children: five-day drug provocation test in the diagnosis of nonimmediate reactions.

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Allergy Unit, Department of Pediatric, Anna Meyer Children's University Hospital, Florence, Italy. Electronic address:
Allergy and Immunology Division, The Children's Hospital of Philadelphia, Pa.
Allergy Unit, Department of Pediatric, Anna Meyer Children's University Hospital, Florence, Italy.



The drug provocation test (DPT) is the gold standard to rule out drug hypersensitivity. There are standardized DPT protocols to diagnose immediate reactions to drugs, but not for nonimmediate reactions.


The aim of this study was to show the sensitivity and specificity of an allergy work-up that included a 5-day DPT in children with histories of nonimmediate reactions to amoxicillin through focusing on a pediatric population with histories of immediate and nonimmediate reactions to amoxicillin.


Two hundred consecutive patients with histories of amoxicillin reactions referred to the Allergy Unit of Anna Meyer Children's Hospital for suspected drug allergy from 2008 to 2011 underwent in vivo tests with the culprit drug according to European Academy of Allergy and Clinical Immunology guidelines. Moreover, most of those children, regardless of the skin tests results, were challenged with amoxicillin for a total of 5 days.


In 4 years, 200 patients were evaluated for a history of drug hypersensitivity to amoxicillin. The majority of patients (76%) had a history of mild nonimmediate reactions. All 200 patients underwent skin tests, and 9 of 200 tested positive. A total of 177 DPTs were performed with amoxicillin for 5 days in each child. Diagnosis of amoxicillin allergy was confirmed by a DPT in 17 patients (9.6%); 14/17 had history of nonimmediate reactions; 4/14 (26.6%) reacted on day 5.


According to our results, a long-term DPT protocol increases the sensitivity of the allergy work-up, and it should be recommended for patients with a history of amoxicillin nonimmediate reaction.


Amoxicillin allergy; Children; Diagnostic work-up; Drug allergy; Drug provocation test; Long-term drug provocation test; Nonimmediate reactions

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