N Franklin Adkinson1, Louis M Mendelson2, Charlotte Ressler3, John C Keogh4. 1. Division of Allergy & Clinical Immunology, Johns Hopkins Asthma & Allergy Center, Baltimore, Maryland; AllerQuest LLC, Plainville, Connecticut. Electronic address: Fadkinso@jhmi.edu. 2. AllerQuest LLC, Plainville, Connecticut; University of Connecticut School of Medicine, New England Food Allergy Center, Farmington, Connecticut. 3. AllerQuest LLC, Plainville, Connecticut; University of Connecticut School of Medicine, Farmington, Connecticut. 4. AllerQuest LLC, Plainville, Connecticut; Keogh Medical Writing, LLC, Guilford, Connecticut.
Abstract
OBJECTIVE: To review the history of the penicillin minor determinants and evaluate their relevance for current diagnosis. DATA SOURCES: Skin testing to detect immunoglobulin E (IgE) sensitivity to penicillins in patients with a history of penicillin allergy has been the subject of more than 55 years of published research involving tens of thousands of patients. STUDY SELECTIONS: Selection of data was based on its relevance to the objective of this article. RESULTS: It was established early on that testing with the major penicilloyl determinant using the polyvalent penicilloyl-polylysine (PPL) is negative in a substantial portion (10% to 64%, including recent increases) of those at risk for immediate hypersensitivity reactions. A variety of minor penicillin determinants are clinically significant in that their use in skin testing is essential to detect all those at risk. In particular, a minor determinant mixture of benzylpenicillin, benzylpenicilloate, and benzylpenilloate, used in conjunction with PPL, has been shown in numerous studies to achieve an average negative predictive value (NPV) of 97.9% in history-positive patients. Benzylpenicillin alone, as the sole minor determinant, leaves many skin test-positive patients undiscovered. Use of amoxicillin as an additional minor determinant reagent appears to identify another 2% to 8% of skin test-positive patients in some populations. CONCLUSION: IgE skin testing, using both the major and appropriate minor determinants of penicillin, can identify, with a high degree of reliability (NPV ∼97%), penicillin allergy history-positive patients who can receive beta-lactam antibiotics without concern for serious acute allergy, including anaphylaxis. The few false-negative skin tests reported globally are largely confined to minor, self-limited cutaneous reactions.
OBJECTIVE: To review the history of the penicillin minor determinants and evaluate their relevance for current diagnosis. DATA SOURCES: Skin testing to detect immunoglobulin E (IgE) sensitivity to penicillins in patients with a history of penicillinallergy has been the subject of more than 55 years of published research involving tens of thousands of patients. STUDY SELECTIONS: Selection of data was based on its relevance to the objective of this article. RESULTS: It was established early on that testing with the major penicilloyl determinant using the polyvalent penicilloyl-polylysine (PPL) is negative in a substantial portion (10% to 64%, including recent increases) of those at risk for immediate hypersensitivity reactions. A variety of minor penicillin determinants are clinically significant in that their use in skin testing is essential to detect all those at risk. In particular, a minor determinant mixture of benzylpenicillin, benzylpenicilloate, and benzylpenilloate, used in conjunction with PPL, has been shown in numerous studies to achieve an average negative predictive value (NPV) of 97.9% in history-positive patients. Benzylpenicillin alone, as the sole minor determinant, leaves many skin test-positive patients undiscovered. Use of amoxicillin as an additional minor determinant reagent appears to identify another 2% to 8% of skin test-positive patients in some populations. CONCLUSION: IgE skin testing, using both the major and appropriate minor determinants of penicillin, can identify, with a high degree of reliability (NPV ∼97%), penicillinallergy history-positive patients who can receive beta-lactam antibiotics without concern for serious acute allergy, including anaphylaxis. The few false-negative skin tests reported globally are largely confined to minor, self-limited cutaneous reactions.
Authors: María Del Valle Campanón Toro; Esther Moreno Rodilla; Alicia Gallardo Higueras; Elena Laffond Yges; Francisco J Muñoz Bellido; María Teresa Gracia Bara; Cristina Martin García; Vidal Moreno Rodilla; Eva M Macías Iglesias; Sonia Arriba Méndez; Miriam Sobrino García; Ignacio Dávila Journal: Biomedicines Date: 2022-06-28