How do you diagnose and treat a patient with a penicillin allergy?

From the Guidelines

Diagnosing a penicillin allergy requires a detailed history of previous reactions and consideration of skin testing or oral challenge testing in a controlled setting. To diagnose a penicillin allergy, obtain a detailed history of previous reactions, including timing, symptoms, and severity. Mild reactions typically involve rash or hives, while severe reactions include anaphylaxis, angioedema, or respiratory distress.

Diagnosis Methods

• Laboratory or in vitro diagnostics (measuring tryptase or specific IgE antibodies, and cellular in vitro testing)
• Penicillin skin testing (PST) (patch test, the skin prick test, and the intradermal test) can detect the presence/absence of specific anti-penicillin IgE antibodies against minor (benzylpenicillin, benzylpenicilloate, and benzylpenilloate) or major determinants (penicilloyl-polyly- sine) 1
• Drug challenge (DC), or graded challenge, or test dosing, can be performed following a negative lab or skin test and will exclude or confirm a penicillin allergy diagnosis 1

Key Considerations

• Less than 5% of individuals labeled with a penicillin allergy are confirmed, with appropriate testing, to have either a currently active acute onset IgE-mediated penicillin allergy or a clinically significant delayed onset T-cell-mediated penicillin hypersensitivity 1
• Many patients labeled as penicillin-allergic may not have true allergies, so periodic reassessment is valuable, as approximately 80% of patients lose their sensitivity over time
• The prevalence of penicillin allergy in much of the world remains unknown, but it is estimated that up to 10% of the population may be labeled as penicillin-allergic 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high rate of positive tests of routine testing can be as high as 5%, and this should be taken into account when interpreting the results of penicillin skin testing 1
• Regional figures for penicillin allergy labeled hospitalized patients from mainland China and Japan ranged from 5 to 5.6% 1
• Up to 6% of a population-based cohort in the UK carried a penicillin allergy label 1
• Just under 10% of individuals who used healthcare in the USA carried a penicillin allergy label 1
• About 12% of a sample of children and adults being seen as outpatients in Belgium carried a penicillin allergy label 1
• Overall, the prevalence of a penicillin allergy label was higher in individuals who actively used healthcare, in females, in hospitalized patients, and increased with increasing age 1
• The prevalence of penicillin allergy in much of the world remains unknown 1
• People who self-report as penicillin allergic based on unspecific reactions in the past, and in the absence of confirmatory testing, frequently do not have a true penicillin allergy 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high rate of positive tests of routine testing can be as high as 5%, and this should be taken into account when interpreting the results of penicillin skin testing 1
• Regional figures for penicillin allergy labeled hospitalized patients from mainland China and Japan ranged from 5 to 5.6% 1
• Up to 6% of a population-based cohort in the UK carried a penicillin allergy label 1
• Just under 10% of individuals who used healthcare in the USA carried a penicillin allergy label 1
• About 12% of a sample of children and adults being seen as outpatients in Belgium carried a penicillin allergy label 1
• Overall, the prevalence of a penicillin allergy label was higher in individuals who actively used healthcare, in females, in hospitalized patients, and increased with increasing age 1
• The prevalence of penicillin allergy in much of the world remains unknown 1
• People who self-report as penicillin allergic based on unspecific reactions in the past, and in the absence of confirmatory testing, frequently do not have a true penicillin allergy 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high rate of positive tests of routine testing can be as high as 5%, and this should be taken into account when interpreting the results of penicillin skin testing 1
• Regional figures for penicillin allergy labeled hospitalized patients from mainland China and Japan ranged from 5 to 5.6% 1
• Up to 6% of a population-based cohort in the UK carried a penicillin allergy label 1
• Just under 10% of individuals who used healthcare in the USA carried a penicillin allergy label 1
• About 12% of a sample of children and adults being seen as outpatients in Belgium carried a penicillin allergy label 1
• Overall, the prevalence of a penicillin allergy label was higher in individuals who actively used healthcare, in females, in hospitalized patients, and increased with increasing age 1
• The prevalence of penicillin allergy in much of the world remains unknown 1
• People who self-report as penicillin allergic based on unspecific reactions in the past, and in the absence of confirmatory testing, frequently do not have a true penicillin allergy 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high rate of positive tests of routine testing can be as high as 5%, and this should be taken into account when interpreting the results of penicillin skin testing 1
• Regional figures for penicillin allergy labeled hospitalized patients from mainland China and Japan ranged from 5 to 5.6% 1
• Up to 6% of a population-based cohort in the UK carried a penicillin allergy label 1
• Just under 10% of individuals who used healthcare in the USA carried a penicillin allergy label 1
• About 12% of a sample of children and adults being seen as outpatients in Belgium carried a penicillin allergy label 1
• Overall, the prevalence of a penicillin allergy label was higher in individuals who actively used healthcare, in females, in hospitalized patients, and increased with increasing age 1
• The prevalence of penicillin allergy in much of the world remains unknown 1
• People who self-report as penicillin allergic based on unspecific reactions in the past, and in the absence of confirmatory testing, frequently do not have a true penicillin allergy 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high rate of positive tests of routine testing can be as high as 5%, and this should be taken into account when interpreting the results of penicillin skin testing 1
• Regional figures for penicillin allergy labeled hospitalized patients from mainland China and Japan ranged from 5 to 5.6% 1
• Up to 6% of a population-based cohort in the UK carried a penicillin allergy label 1
• Just under 10% of individuals who used healthcare in the USA carried a penicillin allergy label 1
• About 12% of a sample of children and adults being seen as outpatients in Belgium carried a penicillin allergy label 1
• Overall, the prevalence of a penicillin allergy label was higher in individuals who actively used healthcare, in females, in hospitalized patients, and increased with increasing age 1
• The prevalence of penicillin allergy in much of the world remains unknown 1
• People who self-report as penicillin allergic based on unspecific reactions in the past, and in the absence of confirmatory testing, frequently do not have a true penicillin allergy 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high rate of positive tests of routine testing can be as high as 5%, and this should be taken into account when interpreting the results of penicillin skin testing 1
• Regional figures for penicillin allergy labeled hospitalized patients from mainland China and Japan ranged from 5 to 5.6% 1
• Up to 6% of a population-based cohort in the UK carried a penicillin allergy label 1
• Just under 10% of individuals who used healthcare in the USA carried a penicillin allergy label 1
• About 12% of a sample of children and adults being seen as outpatients in Belgium carried a penicillin allergy label 1
• Overall, the prevalence of a penicillin allergy label was higher in individuals who actively used healthcare, in females, in hospitalized patients, and increased with increasing age 1
• The prevalence of penicillin allergy in much of the world remains unknown 1
• People who self-report as penicillin allergic based on unspecific reactions in the past, and in the absence of confirmatory testing, frequently do not have a true penicillin allergy 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high rate of positive tests of routine testing can be as high as 5%, and this should be taken into account when interpreting the results of penicillin skin testing 1
• Regional figures for penicillin allergy labeled hospitalized patients from mainland China and Japan ranged from 5 to 5.6% 1
• Up to 6% of a population-based cohort in the UK carried a penicillin allergy label 1
• Just under 10% of individuals who used healthcare in the USA carried a penicillin allergy label 1
• About 12% of a sample of children and adults being seen as outpatients in Belgium carried a penicillin allergy label 1
• Overall, the prevalence of a penicillin allergy label was higher in individuals who actively used healthcare, in females, in hospitalized patients, and increased with increasing age 1
• The prevalence of penicillin allergy in much of the world remains unknown 1
• People who self-report as penicillin allergic based on unspecific reactions in the past, and in the absence of confirmatory testing, frequently do not have a true penicillin allergy 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high rate of positive tests of routine testing can be as high as 5%, and this should be taken into account when interpreting the results of penicillin skin testing 1
• Regional figures for penicillin allergy labeled hospitalized patients from mainland China and Japan ranged from 5 to 5.6% 1
• Up to 6% of a population-based cohort in the UK carried a penicillin allergy label 1
• Just under 10% of individuals who used healthcare in the USA carried a penicillin allergy label 1
• About 12% of a sample of children and adults being seen as outpatients in Belgium carried a penicillin allergy label 1
• Overall, the prevalence of a penicillin allergy label was higher in individuals who actively used healthcare, in females, in hospitalized patients, and increased with increasing age 1
• The prevalence of penicillin allergy in much of the world remains unknown 1
• People who self-report as penicillin allergic based on unspecific reactions in the past, and in the absence of confirmatory testing, frequently do not have a true penicillin allergy 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high rate of positive tests of routine testing can be as high as 5%, and this should be taken into account when interpreting the results of penicillin skin testing 1
• Regional figures for penicillin allergy labeled hospitalized patients from mainland China and Japan ranged from 5 to 5.6% 1
• Up to 6% of a population-based cohort in the UK carried a penicillin allergy label 1
• Just under 10% of individuals who used healthcare in the USA carried a penicillin allergy label 1
• About 12% of a sample of children and adults being seen as outpatients in Belgium carried a penicillin allergy label 1
• Overall, the prevalence of a penicillin allergy label was higher in individuals who actively used healthcare, in females, in hospitalized patients, and increased with increasing age 1
• The prevalence of penicillin allergy in much of the world remains unknown 1
• People who self-report as penicillin allergic based on unspecific reactions in the past, and in the absence of confirmatory testing, frequently do not have a true penicillin allergy 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high rate of positive tests of routine testing can be as high as 5%, and this should be taken into account when interpreting the results of penicillin skin testing 1
• Regional figures for penicillin allergy labeled hospitalized patients from mainland China and Japan ranged from 5 to 5.6% 1
• Up to 6% of a population-based cohort in the UK carried a penicillin allergy label 1
• Just under 10% of individuals who used healthcare in the USA carried a penicillin allergy label 1
• About 12% of a sample of children and adults being seen as outpatients in Belgium carried a penicillin allergy label 1
• Overall, the prevalence of a penicillin allergy label was higher in individuals who actively used healthcare, in females, in hospitalized patients, and increased with increasing age 1
• The prevalence of penicillin allergy in much of the world remains unknown 1
• People who self-report as penicillin allergic based on unspecific reactions in the past, and in the absence of confirmatory testing, frequently do not have a true penicillin allergy 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high rate of positive tests of routine testing can be as high as 5%, and this should be taken into account when interpreting the results of penicillin skin testing 1
• Regional figures for penicillin allergy labeled hospitalized patients from mainland China and Japan ranged from 5 to 5.6% 1
• Up to 6% of a population-based cohort in the UK carried a penicillin allergy label 1
• Just under 10% of individuals who used healthcare in the USA carried a penicillin allergy label 1
• About 12% of a sample of children and adults being seen as outpatients in Belgium carried a penicillin allergy label 1
• Overall, the prevalence of a penicillin allergy label was higher in individuals who actively used healthcare, in females, in hospitalized patients, and increased with increasing age 1
• The prevalence of penicillin allergy in much of the world remains unknown 1
• People who self-report as penicillin allergic based on unspecific reactions in the past, and in the absence of confirmatory testing, frequently do not have a true penicillin allergy 1
• Removing incorrect penicillin allergy labels (i.e., penicillin allergy delabeling) is of importance to improve antimicrobial stewardship practices worldwide 1
• Delabeling can be done through oral administration of a low-dose penicillin in low-risk penicillin allergy patients, and, on some occasions, may be done directly by clinical history taking alone 1
• Testing for penicillin allergy could be an approach to optimize antibiotic selection and improve patient safety by preventing allergic reactions 1
• Anaphylaxis and death following penicillin administration is of special concern, and the mechanism for anaphylaxis is IgE-mediated 1
• Risk factors associated with IgE-mediated reactions include age, presence of allergic diseases, and multiple short courses (mainly if parenteral or topic) 1
• The current practices for testing patients with a reported penicillin allergy vary, but skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Experts estimate that testing with only the major determinant and penicillin G identifies 90%-97% of the currently allergic patients, but skin testing without the minor determinants would still miss 3%-10% of allergic patients 1
• Serious or fatal reactions can occur among these minor-determinant-positive patients, so experts suggest caution when the full battery of skin-test reagents is not available 1
• With the passage of time after an allergic reaction to penicillin, most persons who have had a severe reaction stop expressing penicillin-specific IgE, and these persons can be treated safely with penicillin 1
• The results of many investigations indicate that skin testing with the major and minor determinants can reliably identify persons at high risk for penicillin reactions 1
• Although these reagents are easily generated and have been available in academic centers for greater than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen, the major determinant) and penicillin G are available commercially 1
• An estimated 10% of persons who report a history of severe allergic reactions to penicillin are still allergic 1
• Allergic reactions are amplified reactions due to an immune mechanism to an otherwise harmless and exogenous compound, and depending on the timing following contact with the compound, these can be immediate (<1 h: urticaria, angioedema, and anaphylaxis), accelerated (1 to 72 h: urticaria and maculopapular rashes), or late (>72 h: skin rashes, erythema multiforme, serum sickness, and hemolytic anemia) 1
• The possibility of a false positive penicillin skin test also has to be considered, and false-positives can be due to test (e.g., 3-mm wheal threshold, higher concentrations of reagents, or improper preparation or storage) or patient factors (e.g., female sex) 1
• A positive reaction presents as redness, itchiness, and a raised bump, and a positive result indicates a high likelihood of penicillin allergy 1
• The high

From the Research

Diagnosis of Penicillin Allergy

• Penicillin allergy is diagnosed through a combination of medical history, physical examination, and testing, including skin testing and graded challenge 2, 3.
• The evaluation of penicillin allergy is important for antimicrobial stewardship, as reported allergy to penicillin can lead to the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance 2.
• Patients with a low-risk history of penicillin allergy, such as those with isolated nonallergic symptoms or a family history of penicillin allergy, can undergo direct amoxicillin challenge 2.
• Moderate-risk patients can be evaluated with penicillin skin testing, which has a negative predictive value that exceeds 95% and approaches 100% when combined with amoxicillin challenge 2.

Testing for Penicillin Allergy

• Penicillin skin testing is a useful tool for evaluating penicillin allergy, but its results must be interpreted in the context of the patient's medical history and physical examination 4, 5.
• A positive skin test result or specific IgE to penicillin does not reliably predict penicillin allergy, and a combination of positive case history with simultaneous positive skin test result and specific IgE or a positive challenge result is the best predictor of a clinically significant penicillin allergy 5.
• Graded challenge and desensitization may be used in some cases where treatment with penicillins is essential 3, 6.

Classification of Penicillin Allergy

• Penicillin allergy can be classified into different types, including IgE-mediated and non-IgE-mediated reactions, based on the clinical presentation and physical examination findings 3, 6.
• The classification of penicillin allergy is important for determining the appropriate treatment and management strategy, including the use of alternative antibiotics or desensitization 3, 6.