Strategies to identify and prevent penicillin allergy mislabeling and appropriately de-label patients

Documentation at the time of the reaction, within the encounter note and the allergy tab, is essential, so that other physicians caring for the patient, in the future, will be knowledgeable about the details of the reaction. Make it your responsibility to accurately document penicillin allergy in patients’ charts, including removing the “penicillin allergy” label from the chart of patients whose history is inconsistent with allergy, who have tolerated subsequent courses of the same penicillin derivative, or who have passed testing in an allergist’s office. In a study of 639 patients who tested negative for penicillin allergy, 51% still had a “penicillin allergy” label in their chart more than 4 years later.³⁶

Penicillin allergy evaluation. When a patient cannot be cleared of a “penicillin allergy” label by history alone, and in the absence of severe features such as mucous membrane involvement, they should be further evaluated through objective testing for potential IgE-mediated allergy. This assessment includes penicillin skin testing or an oral challenge, or both.

Skin testing involves skin-prick testing of major and minor determinants of penicillin; when skin-prick testing is negative, intradermal testing of major and minor determinants should follow. The negative predictive value of penicillin skin testing is high: In a prospective, multicenter investigation, researchers demonstrated that, when both the major penicillin determinant and a minor determinant mixture were used, negative predictive value was 97.9%.³⁷

Rashes manifesting during the first hours after exposure are more likely to be IgE mediated, particularly when accompanied by other systemic symptoms; consider them a high-risk sign.

However, a minor determinant mixture is not commercially available in the United States; therefore, penicillin G is often used alone as the minor determinant. Typically, if a patient passes skin testing, a challenge dose of penicillin or amoxicillin is administered, followed by an observation period. The risk of re-sensitization after oral penicillin is thought to be low and does not preclude future use.³⁸

Although drug testing is most often performed in an allergist’s office, several groups have developed protocols that allow for limited testing of low-risk patients in a primary care setting.^8,31 For example, several studies have demonstrated that patients presenting with low-risk skin rash can be safely tested with a supervised oral challenge alone.^18,28 The FIGURE^{8,27,30,31,33,34} outlines our proposed workflow for risk stratification and subsequent management of patients with a “penicillin allergy” label.

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