Antibiotic Allergy in Pediatrics Abstract the Overlabeling of Pediatric Antibiotic Allergy Represents a Huge Burden NIH in Society
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Allison Eaddy Norton, MD, a Katherine Konvinse, MS, b Elizabeth J. Phillips, MD, a, b, c, d, e Ana Dioun Broyles, MDf Antibiotic Allergy in Pediatrics abstract The overlabeling of pediatric antibiotic allergy represents a huge burden NIH in society. Given that up to 10% of the US population is labeled as penicillin allergic, it can be estimated that at least 5 million children in this country are labeled with penicillin allergy. We now understand that most of the – aDivision of Allergy, Immunology and Pulmonology, cutaneous symptoms that are interpreted as drug allergy are likely Monroe Carell Jr. Children's Hospital at Vanderbilt, and viral induced or due to a drug virus interaction, and they usually do not cJohn A. Oates Institute for Experimental Therapeutics and Department of Pharmacology, School of Medicine, represent a long-lasting, drug-specific, adaptive immune response to the Vanderbilt University School of Medicine, Nashville, antibiotic that a child received. Because most antibiotic allergy labels Tennessee; Departments of dDivision of Infectious Disease, Medicine and bPathology, Microbiology, and Immunology, acquired in childhood are carried into adulthood, the overlabeling of Vanderbilt University Medical Center, Nashville, Tennessee; antibiotic allergy is a liability that leads to unnecessary long-term health eInstitute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia; and fDivision of Allergy and care risks, costs, and antibiotic resistance. Fortunately, awareness of this Immunology, Boston Children’s Hospital, Harvard Medical growing burden is increasing and leading to more emphasis on antibiotic School, Boston, Massachusetts allergy delabeling strategies in the adult population. There is growing Dr Norton conceptualized and outlined the article, literature that is used to support the safe and efficacious use of tools such drafted the initial manuscript, and reviewed and as skin testing and drug challenge to evaluate and manage children with revised the manuscript; Ms Konvinse aided in the conception and outline of the article, drafted antibiotic allergy labels. In addition, there is an increasing understanding of sections of the article, and reviewed and revised antibiotic reactivity within classes and side-chain reactions. In summary, a the manuscript; Drs Phillips and Broyles aided better overall understanding of the current tools available for the diagnosis in conceptualizing and outlining the article, and and management of adverse drug reactions is likely to change how pediatric critically reviewed and revised the manuscript; and all authors approved the final manuscript primary care providers evaluate and treat patients with such diagnoses and as submitted and agree to be accountable for all prevent the unnecessary avoidance of antibiotics, particularly penicillins. aspects of the work. DOI: https:// doi. org/ 10. 1542/ peds. 2017- 2497 1 Accepted for publication Dec 13, 2017 Antibiotic allergy labeling leads to their third birthday. The prevalent Address correspondence to Allison Eaddy Norton, significant individual and public health carriage of these childhood allergy MD, Division of Pediatric Allergy, Immunology, consequences. Unlike vaccination, labels into adulthood perpetuates and Pulmonology, Vanderbilt Children’s Hospital, there is no systematic approach to the use of alternative antibiotics, Vanderbilt University, 2200 Children’s Way, 11215 DOT, Nashville, TN 37232. E-mail: allison.norton@ address antibiotic allergy during which are often more expensive, vanderbilt.edu routine office visits, and allergy labels less effective,– and contribute to PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, persist into adulthood. Antibiotic an increase2 4 in antibiotic-resistant 1098-4275). allergy usually comes to light when bacteria. However, studies reveal Copyright © 2018 by the American Academy of treatment is imminent, and physicians that when children are tested and/– Pediatrics often find themselves choosing or undergo drug challenging, >90% 5 7 FINANCIAL DISCLOSURE: Dr Phillips has received more expensive and time-intensive are able to tolerate the antibiotic. consultancy fees from Xcovery and BioCryst; Drs procedures, such as desensitization, Unfortunately, even when the Norton, Konvinse, and Broyles have indicated they or using higher-cost alternative diagnosis of drug allergy is excluded by have no financial relationships relevant to this antibiotics with potentially more side such procedures, not only parents but article to disclose. effects. These measures may satisfy the many providers are still8, resistant 9 to FUNDING: Ms Konvinse is supported by the National immediate need for treatment but do drug allergy delabeling. Institutes of Health (1P50GM115305, 2T32GM7347, not address the primary problem. and F30 AI131780). Dr Phillips is supported by Prescription costs are 30% to 40% 1P50GM115305-01, 1R01AI103348-01, 1P30AI110527- Antibiotic allergy labels are often higher in patients10 with suspected 01A1, 5T32AI007474-20, and 1 R13AR71267-01 from acquired because of rashes reported penicillin allergy. If just half of by parents, and most children never the children who visit a physician To cite: Norton AE, Konvinse K, Phillips EJ, et al. undergo an allergy evaluation to for acute otitis media annually Antibiotic Allergy in Pediatrics. Pediatrics. 2018; address the diagnosis. In a recent were to receive amoxicillin instead 141(5):e20172497 study, 75% of children diagnosed with of cefdinir (a common alternative penicillin allergy were labeled before prescribed for treating patients with Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 141, number 5, May 2018:e20172497 STATE-OF-THE-ART REVIEW ARTICLE a history of penicillin allergy), the Researchers in 1 large study in the adults and children– and is as high estimated annual savings11 would United States evaluating 411 543 as 20% in those18,38 linked41 to ongoing exceed $34 million. Researchers adult and pediatric medical records medical care. An allergy to in a recent cohort study were able found that the overall incidence amoxicillin is the most32 common drug to match 51582 subjects with and of self-reported antibiotic24 allergy allergy in children. Although the without penicillin allergy at hospital was as high as 15.3%. Despite epidemiology in the United States is admission. It confirmed that patients the high number of reported cases, currently unknown, hypersensitivity who require alternative drugs, such <10% of cases– are confirmed to to clavulanic acid appears prevalent as fluoroquinolones, clindamycin,Clostridium and be allergic25 after31 testing and/or in southern Europe and26, 42,has 43 been difficilevancomycin, because of a penicillin challenge, indicating that true described in children. allergy haveStaphylococcus 23.4% more aureus allergy to antibiotics32, 33 is rare and Of ADRs in pediatric patients, –β , 14.1% more methicillin- overdiagnosed. 23% are reported to be caused by resistant , and The drug allergy box is the major non -lactam antibiotics. Although 30.1% more vancomycin-resistant place in most medical records where rarely confirmed in pediatric enterococci infections compared 4 ADRs are documented, often without studies, macrolides are reported to with controls. The accumulation of reference to the immunologic basis cause drug allergy, mostly44 benign adverse drug labels is more limiting of the reaction. This label does not cutaneous reactions. Among in populations that are susceptible typically discriminate between macrolides, the 15-membered ring to frequent infections, such as cystic – pharmacological effects, side effects, azalide (azithromycin) may be more fibrosis, particularly when drug 12 14 temporally associated observations, allergenic than clarithromycin and resistance develops. or true drug allergies, making without consistent cross-reactivity with clarithromycin, erythromycin, In this state-of-the-art review, we aim the drug allergy box subject to 34 to provide clinicians with an evidence- overestimation of true allergy risk. and other 14-membered45, 46 ring based toolbox for the diagnostic traditional macrolides. This overestimation has been workup of children with antibiotic Sulfonamide antimicrobial agents demonstrated in multiple studies in infrequently cause IgE-mediated allergy. The ultimate goal is to improve – which the initial drug allergy label was patient and provider education to symptoms in children but are known based on questionnaires and/or the address and reconcile allergy labels to cause a wide array of T-cell opinions of experienced physicians, early to prevent children from carrying mediated symptoms, most commonly but subsequent drug challenges these potentially false antibiotic allergy – mild cutaneous exanthems, but were used to disprove the majority labels into adulthood. 35 37 more severe reactions such as of them. In a large study of drug reaction with eosinophilia EPIDEMIOLOGY OF ANTIBIOTIC consecutive patients with or without ALLERGY and systemic symptoms (DRESS) a history of penicillin allergy, the rate syndrome, fixed drug eruption, of positive skin testing results in those Stevens-Johnson syndrome (SJS), who were labeled as penicillin allergic toxic epidermal necrolysis (TEN), Epidemiologic studies in children with vague histories was 1.7%, which drug-induced liver disease, and with antibiotic allergy are scarce is the same as in those without23 a cytopenia– have been reported as and fraught with