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The malady of penicillin allergy
Ann Allergy Asthma Immunol 116 (2016) 269e270
Contents lists available at ScienceDirect
Guest Editorial
The malady of penicillin allergy Penicillin allergy is a malady that has only recently been fully appreciated. When patients who furnish a history of allergy to penicillin or a penicillin-like drug require antibiotic administration for infection or surgical prophylaxis, an alternative noneb-lactam antibiotic (eg, a carbapenem, a quinolone, a macrolide, or vancomycin) is commonly prescribed. These alternative agents can be associated with greater cost, heightened risk for untoward effects, and increased rates of resistant nosocomial organisms, including methicillin-resistant Staphylococcus aureus and vancomycinresistant enterococci, as well as greater risk for developing Clostridium difficile.1 When skin testing is performed to rule out immediate hypersensitivity to penicillin in patients with suspected allergy to penicillin or penicillin-like drugs, skin test results are negative in approximately 90% of such patients.2 In our experience at Cleveland Clinic, the negative predictive value of penicillin skin testing is 99.3%.3 Immediate hypersensitivity skin testing to penicillin can be accomplished with minimal risk. We have reported that penicillin skin testing can be performed safely even in pregnant women with Streptococcus B infection4 and in patients who require organ (eg, lung, liver, heart) transplants.5 Patients with negative skin test results can receive penicillin or a penicillin-like drug without elevated risk for IgE-mediated (allergic or anaphylactic) reaction compared with the general population.2 In this issue of the Annals, Silverman and Apter6 describe a retrospective record review performed at the University of Pennsylvania in which they found a higher prevalence of self-reported allergy to penicillin and penicillin-like drugs (amoxicillin, amoxicillin-clavulanate, or piperacillin-tazobactam) in patients with chronic urticaria and also a higher prevalence of chronic urticaria in patients with self-reported allergy to penicillin and penicillin-like drugs. A co-occurrence or correlation of these 2 conditions, chronic urticaria and penicillin allergy, has been recognized previously. A correlation exists when 2 or more events may be associated with each other but are not necessarily connected by a cause-effect relationship; however, it is a well-known tendency to suspect or assume causality when a correlation is present. Examples of this tendency of which we are all aware include misattributions of causality for vaccines in children with autism.7 In the past, the association of chronic urticaria and penicillin allergy was assumed to be causal. Several decades ago, it was not uncommon for patients with chronic urticaria and a history of penicillin allergy to undergo skin testing to provide substantiation for a suspected role Disclosures: Author has nothing to disclose. Funding Sources: This article has been supported by the William O. Wagner Research and Education Fund, Department of Allergy and Clinical Immunology, Respiratory Institute, Cleveland Clinic.
of consuming foods and beverages (eg, dairy products) that contain small amounts of penicillin as a provoking or perpetuating factor for chronic urticaria. In their classic series of 554 patients with chronic urticaria, Champion et al8 reported that in 21% of cases a cause was established. In 17 (3%) of 554, the cause was allergic urticaria, of which “4 were known to be penicillin sensitive and their chronic urticaria could have been attributed to ingestion of traces of penicillin, although we have no proof of this [italics added].” It is instructive to recall another report from Philadelphia published almost a half-century ago.9 Medical (hospital staff and medical students) and nonmedical (graduate and undergraduate students) subjects at Temple University were enrolled in a study in which they were surveyed to obtain information on the frequency of symptoms often described as adverse effects of medications, occurring in individuals who were taking no medications. Individuals indicated which of the symptoms listed on a questionnaire they had experienced during the prior 72 hours. Those who either had an illness or were taking medication were excluded. The percentages of healthy adults reporting a wide variety of symptoms are shown in Figure 1, with the medical and nonmedical groups combined because the rates were comparable. Similar findings have been reported in individuals taking placebos in the context of clinical trials. Exposure to a placebo may accentuate the severity of symptoms that were preexisting before participation and in some individuals can elicit symptoms not present previously.10 The misattribution of symptoms reflecting a nonallergic drug reaction is not limited to penicillin and nonallergic drug reactions. Silverman and Apter6 found a rate of other drug allergies to any antibiotic of 41% and to other drug allergies of 71%. The National Quality Forum recently launched an antibiotic stewardship initiative to identify best practices for combating inappropriate antibiotic use to improve patient care outcomes and population health.11 A National Action Plan was also issued by President Obama to support World Health Assembly resolution 67.25, which urges countries to take urgent action at the national, regional, and local levels to combat antibiotic resistance.12 The Choosing Wisely program of the American Board of Internal Medicine Foundation recommended in 2014 that physicians not overprescribe noneb-lactam antibiotics to patients with a history of penicillin allergy, without an appropriate evaluation.13 We recognize many of the symptoms shown in Figure 1 as those frequently described by patients with a history of allergy to penicillin or penicillin-like drugs, which in many cases have served to prevent such patients from receiving b-lactam antibiotics for years or even decades. The report in this issue of the Annals6 should prompt allergists-immunologists to be vigilant in identifying patients with a history of penicillin allergydeven if it is not the primary reason for the patient encounter and
http://dx.doi.org/10.1016/j.anai.2016.02.009 1081-1206/Ó 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
270
Guest Editorial / Ann Allergy Asthma Immunol 116 (2016) 269e270
1
Excessive bleeding from gums aŌer brushing teeth Bleeding from gums aŌer brushing teeth Bleeding or bruising Nasal congesƟon Pain in muscles Pain in joints Fever Headaches Faintness or dizziness on first standing up Giddiness or weakness PalpitaƟons ConsƟpaƟon Diarrhea VomiƟng Nausea Dry mouth Loss of appeƟte Insomnia Irritability Inability to concentrate FaƟgue Excessive sleepiness Bad dreams UrƟcaria Rash
21 3 23 10 7 2 14 5 2 3 4 4 0 3 4 4 8 19 26
39 23 6 3 6
0
10
20
30
40
Individuals With Symptoms % Figure 1. Percentage of 414 healthy adults reporting symptoms compatible with nonallergic drug reactions in a 72-hour period.
particularly if the patient is being seen for chronic urticariadto propose skin testing to rule out or confirm the presence of IgEmediated potential to penicillin. The malady of penicillin allergy in most cases is not incurable. Evidence indicates that in most of these patients routine performance of penicillin skin testing will lead to removing the label of penicillin allergy, thereby encouraging improved health care outcomes and demonstrating the value of allergy/immunology care. David M. Lang, MD Cleveland Clinic Department of Allergy and Clinical Immunology Respiratory Institute, Cleveland, OH [email protected]
References [1] Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study. J Allergy Clin Immunol. 2014;133:790e796. [2] Solensky R, Khan DA, Bernstein IL, et al. Drug allergy: an updated parameter. Ann Allergy Asthma Immunol. 2010;105:259e273.
[3] Alvarez del Real G, Rose ME, Ramirez-Atamoros MT, et al. Penicillin skin testing in patients with a history of beta-lactam allergy. Ann Allergy Asthma Immunol. 2007;98:355e359. [4] Philipson E, Lang D, Gordon S, Burlingame J, Emery S, Arroliga M. Management of group B Streptococcus in pregnant women with penicillin allergy. J Reprod Med. 2007;52:480e484. [5] Gutta R, Radojicic C. Safety and effectiveness of penicillin allergy evaluation in the pre-lung transplant patient population. J Allergy Clin Immunol. 2012;129: A102. [6] Silverman S, Localio R, Apter AJ. Association between chronic urticaria and self reported penicillin allergy. Ann Allergy Asthma Immunol. 2016;116: 317e320. [7] Autistic spectrum disorder: no causal relationship with vaccines. Paediatr Child Health. 2007;12:393e395. [8] Champion RH, Roberts SOB, Carpenter RG, Roger JH. Urticaria and angioedema: a review of 554 patients. Br J Derm. 1969;81:588e597. [9] Reidenberg M, Lowenthal D. Adverse non-drug reactions. N Engl J Med. 1968; 279:678e679. [10] Green DM. Pre-existing conditions, placebo reactions, and side effects. Ann Intern Med. 1964;60:255e265. [11] http://www.qualityforum.org/News_And_Resources/Press_Releases/2015/ NQF_Launches_Antibiotic_Stewardship_Initiative.aspx. Accessed January 24, 2016. [12] https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_ for_combating_antibotic-resistant_bacteria.pdf. Accessed January 24, 2016. [13] http://www.choosingwisely.org/wp-content/uploads/2015/01/Choosing-Wis ely-Recommendations.pdf. Accessed January 24, 2016.
Contents lists available at ScienceDirect
Guest Editorial
The malady of penicillin allergy Penicillin allergy is a malady that has only recently been fully appreciated. When patients who furnish a history of allergy to penicillin or a penicillin-like drug require antibiotic administration for infection or surgical prophylaxis, an alternative noneb-lactam antibiotic (eg, a carbapenem, a quinolone, a macrolide, or vancomycin) is commonly prescribed. These alternative agents can be associated with greater cost, heightened risk for untoward effects, and increased rates of resistant nosocomial organisms, including methicillin-resistant Staphylococcus aureus and vancomycinresistant enterococci, as well as greater risk for developing Clostridium difficile.1 When skin testing is performed to rule out immediate hypersensitivity to penicillin in patients with suspected allergy to penicillin or penicillin-like drugs, skin test results are negative in approximately 90% of such patients.2 In our experience at Cleveland Clinic, the negative predictive value of penicillin skin testing is 99.3%.3 Immediate hypersensitivity skin testing to penicillin can be accomplished with minimal risk. We have reported that penicillin skin testing can be performed safely even in pregnant women with Streptococcus B infection4 and in patients who require organ (eg, lung, liver, heart) transplants.5 Patients with negative skin test results can receive penicillin or a penicillin-like drug without elevated risk for IgE-mediated (allergic or anaphylactic) reaction compared with the general population.2 In this issue of the Annals, Silverman and Apter6 describe a retrospective record review performed at the University of Pennsylvania in which they found a higher prevalence of self-reported allergy to penicillin and penicillin-like drugs (amoxicillin, amoxicillin-clavulanate, or piperacillin-tazobactam) in patients with chronic urticaria and also a higher prevalence of chronic urticaria in patients with self-reported allergy to penicillin and penicillin-like drugs. A co-occurrence or correlation of these 2 conditions, chronic urticaria and penicillin allergy, has been recognized previously. A correlation exists when 2 or more events may be associated with each other but are not necessarily connected by a cause-effect relationship; however, it is a well-known tendency to suspect or assume causality when a correlation is present. Examples of this tendency of which we are all aware include misattributions of causality for vaccines in children with autism.7 In the past, the association of chronic urticaria and penicillin allergy was assumed to be causal. Several decades ago, it was not uncommon for patients with chronic urticaria and a history of penicillin allergy to undergo skin testing to provide substantiation for a suspected role Disclosures: Author has nothing to disclose. Funding Sources: This article has been supported by the William O. Wagner Research and Education Fund, Department of Allergy and Clinical Immunology, Respiratory Institute, Cleveland Clinic.
of consuming foods and beverages (eg, dairy products) that contain small amounts of penicillin as a provoking or perpetuating factor for chronic urticaria. In their classic series of 554 patients with chronic urticaria, Champion et al8 reported that in 21% of cases a cause was established. In 17 (3%) of 554, the cause was allergic urticaria, of which “4 were known to be penicillin sensitive and their chronic urticaria could have been attributed to ingestion of traces of penicillin, although we have no proof of this [italics added].” It is instructive to recall another report from Philadelphia published almost a half-century ago.9 Medical (hospital staff and medical students) and nonmedical (graduate and undergraduate students) subjects at Temple University were enrolled in a study in which they were surveyed to obtain information on the frequency of symptoms often described as adverse effects of medications, occurring in individuals who were taking no medications. Individuals indicated which of the symptoms listed on a questionnaire they had experienced during the prior 72 hours. Those who either had an illness or were taking medication were excluded. The percentages of healthy adults reporting a wide variety of symptoms are shown in Figure 1, with the medical and nonmedical groups combined because the rates were comparable. Similar findings have been reported in individuals taking placebos in the context of clinical trials. Exposure to a placebo may accentuate the severity of symptoms that were preexisting before participation and in some individuals can elicit symptoms not present previously.10 The misattribution of symptoms reflecting a nonallergic drug reaction is not limited to penicillin and nonallergic drug reactions. Silverman and Apter6 found a rate of other drug allergies to any antibiotic of 41% and to other drug allergies of 71%. The National Quality Forum recently launched an antibiotic stewardship initiative to identify best practices for combating inappropriate antibiotic use to improve patient care outcomes and population health.11 A National Action Plan was also issued by President Obama to support World Health Assembly resolution 67.25, which urges countries to take urgent action at the national, regional, and local levels to combat antibiotic resistance.12 The Choosing Wisely program of the American Board of Internal Medicine Foundation recommended in 2014 that physicians not overprescribe noneb-lactam antibiotics to patients with a history of penicillin allergy, without an appropriate evaluation.13 We recognize many of the symptoms shown in Figure 1 as those frequently described by patients with a history of allergy to penicillin or penicillin-like drugs, which in many cases have served to prevent such patients from receiving b-lactam antibiotics for years or even decades. The report in this issue of the Annals6 should prompt allergists-immunologists to be vigilant in identifying patients with a history of penicillin allergydeven if it is not the primary reason for the patient encounter and
http://dx.doi.org/10.1016/j.anai.2016.02.009 1081-1206/Ó 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
270
Guest Editorial / Ann Allergy Asthma Immunol 116 (2016) 269e270
1
Excessive bleeding from gums aŌer brushing teeth Bleeding from gums aŌer brushing teeth Bleeding or bruising Nasal congesƟon Pain in muscles Pain in joints Fever Headaches Faintness or dizziness on first standing up Giddiness or weakness PalpitaƟons ConsƟpaƟon Diarrhea VomiƟng Nausea Dry mouth Loss of appeƟte Insomnia Irritability Inability to concentrate FaƟgue Excessive sleepiness Bad dreams UrƟcaria Rash
21 3 23 10 7 2 14 5 2 3 4 4 0 3 4 4 8 19 26
39 23 6 3 6
0
10
20
30
40
Individuals With Symptoms % Figure 1. Percentage of 414 healthy adults reporting symptoms compatible with nonallergic drug reactions in a 72-hour period.
particularly if the patient is being seen for chronic urticariadto propose skin testing to rule out or confirm the presence of IgEmediated potential to penicillin. The malady of penicillin allergy in most cases is not incurable. Evidence indicates that in most of these patients routine performance of penicillin skin testing will lead to removing the label of penicillin allergy, thereby encouraging improved health care outcomes and demonstrating the value of allergy/immunology care. David M. Lang, MD Cleveland Clinic Department of Allergy and Clinical Immunology Respiratory Institute, Cleveland, OH [email protected]
References [1] Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study. J Allergy Clin Immunol. 2014;133:790e796. [2] Solensky R, Khan DA, Bernstein IL, et al. Drug allergy: an updated parameter. Ann Allergy Asthma Immunol. 2010;105:259e273.
[3] Alvarez del Real G, Rose ME, Ramirez-Atamoros MT, et al. Penicillin skin testing in patients with a history of beta-lactam allergy. Ann Allergy Asthma Immunol. 2007;98:355e359. [4] Philipson E, Lang D, Gordon S, Burlingame J, Emery S, Arroliga M. Management of group B Streptococcus in pregnant women with penicillin allergy. J Reprod Med. 2007;52:480e484. [5] Gutta R, Radojicic C. Safety and effectiveness of penicillin allergy evaluation in the pre-lung transplant patient population. J Allergy Clin Immunol. 2012;129: A102. [6] Silverman S, Localio R, Apter AJ. Association between chronic urticaria and self reported penicillin allergy. Ann Allergy Asthma Immunol. 2016;116: 317e320. [7] Autistic spectrum disorder: no causal relationship with vaccines. Paediatr Child Health. 2007;12:393e395. [8] Champion RH, Roberts SOB, Carpenter RG, Roger JH. Urticaria and angioedema: a review of 554 patients. Br J Derm. 1969;81:588e597. [9] Reidenberg M, Lowenthal D. Adverse non-drug reactions. N Engl J Med. 1968; 279:678e679. [10] Green DM. Pre-existing conditions, placebo reactions, and side effects. Ann Intern Med. 1964;60:255e265. [11] http://www.qualityforum.org/News_And_Resources/Press_Releases/2015/ NQF_Launches_Antibiotic_Stewardship_Initiative.aspx. Accessed January 24, 2016. [12] https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_ for_combating_antibotic-resistant_bacteria.pdf. Accessed January 24, 2016. [13] http://www.choosingwisely.org/wp-content/uploads/2015/01/Choosing-Wis ely-Recommendations.pdf. Accessed January 24, 2016.