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• W2956044946 abstract "A father brings his 2 sons, ages 11 and 13 years, to an allergy clinic for testing for amoxicillin allergy. They both received amoxicillin for upper respiratory infections as toddlers, and one of them developed diarrhea. Both were labeled as penicillin allergic, but the family says both they and the pediatrician have forgotten who actually had the reaction. Their charts both carry the label of penicillin allergy. A 4-year-old girl presents to an allergy clinic for evaluation of allergic rhinitis. Along with year-round nasal congestion, she has had nearly monthly ear and sinus infections and has had tympanostomy tubes placed. When she was 2 years old, she developed a maculopapular rash 7 days into a course of amoxicillin, and her sinus infections since then have been treated with azithromycin. The rash with amoxicillin at age 2 was flat and nonmobile, “not exactly hives, but it was itchy.” Her mother is concerned that her daughter will have a life-threatening reaction if she tries amoxicillin again and declines amoxicillin testing. Another child, a 15-year-old boy with cystic fibrosis, presents to an allergy clinic for evaluation of multiple drug allergies. He has a vague history of rashes with amoxicillin and cefdinir, and a history of anaphylaxis with sulfamethoxazole and trimethoprim (Bactrim). He has had recent sinus infections and multiple sputum samples growing methicillin-sensitive Staphylococcus aureus. His pulmonologist would like to treat him with amoxicillin clavulanic acid. Allergists would be happy to see every child with a penicillin allergy if the scale of the problem was not so enormous. Many people, currently up to 10% of the US population or roughly 30 million people, endorse allergies to penicillin.1Solensky R. Khan D.A. Bernstein I.L. et al.Joint Task Force on Practice ParametersAmerican Academy of Allergy, Asthma and ImmunologyAmerican College of Allergy, Asthma and ImmunologyJoint Council of Allergy, Asthma and ImmunologyDrug allergy: an updated practice parameter.Ann Allergy Asthma Immunol. 2010; 105: 259-273Abstract Full Text Full Text PDF PubMed Scopus (589) Google Scholar The evaluation of this many patients in specialty offices is not possible, and may not actually be necessary, because more than 90% of these patients can tolerate penicillin when tested.1Solensky R. Khan D.A. Bernstein I.L. et al.Joint Task Force on Practice ParametersAmerican Academy of Allergy, Asthma and ImmunologyAmerican College of Allergy, Asthma and ImmunologyJoint Council of Allergy, Asthma and ImmunologyDrug allergy: an updated practice parameter.Ann Allergy Asthma Immunol. 2010; 105: 259-273Abstract Full Text Full Text PDF PubMed Scopus (589) Google Scholar New strategies are needed to prevent labeling in the first place and possibly delabel more allergies outside of the specialty office. The 3 cases described exemplify the diversity of situations clinicians encounter during the evaluation of penicillin allergies. Some families have little information about the initial reaction, but the symptoms were mild and unlikely allergic, as in the first scenario. Some children would undoubtedly benefit from access to amoxicillin as the best treatment for ear and sinus infections, but families are hesitant to test penicillins, as in the second case. The final case highlights the existence of subgroups of children who are thought to have a higher risk of reaction; eg, children with cystic fibrosis who have been exposed to more antibiotics and may have a higher likelihood of true allergy, as further discussed elsewhere in this article.2Parmer J.S. Nasser S. Antibiotic allergy in cystic fibrosis.Thorax. 2005; 60: 517-520Google Scholar Some children are at a theoretically increased risk for anaphylaxis, such as those with cardiac disease or severe asthma, or are on immunosuppressive regimens for autoimmunity, both of which complicate penicillin allergy evaluation. We have 3 goals. First, we seek to provide a framework for who should be referred to an allergist vs who could safely receive penicillin at home. Second, we convey information from an allergist's perspective that may be helpful to families being referred about what to expect and how we are beginning to make evaluation easier by being more selective about who needs skin testing. Finally, the third goal is to review advances and new directions in the prediction of risk for severe delayed reactions as a model for what may be possible to do for penicillin allergies in the future. The discovery of penicillin by Alexander Fleming in 1928 was a revolution in medicine. Life expectancy in 1900 was 46.3 and 48.3 years for males and females, respectively.3Centers for Disease Control and Prevention (CDC) Life expectancy.www.cdc.gov/nchs/fastats/life-expectancy.htmGoogle Scholar Access to antibiotics and vaccination has greatly decreased the spread of many infectious diseases, extending our life expectancy and increasing the prevalence of chronic rather than infectious disease. Despite these advances, troublingly few new antibiotics have been discovered over the last decade, and the World Health Organization stated in 2017 that new developments are insufficient to keep up with resistance.4World Health Organization (WHO). Antibacterial agents in clinical development.www.who.int/medicines/areas/rational_use/antibacterial_agents_clinical_development/en/Date: 2017Google Scholar Thankfully, penicillin remains the best treatment for several common pediatric infections, allowing us to hold other antibiotics in reserve. However, its impact has been lessened, insidiously, by erroneously labeled allergies to penicillin and its relatives amoxicillin and amoxicillin clavulanic acid. Multiple studies have shown that there are significant health and financial costs to maintaining an inaccurate allergy.5Macy E. Contreras R. Healthcare utilization and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study.J Allergy Clin Immunol. 2014; 133: 790-796Abstract Full Text Full Text PDF PubMed Scopus (404) Google Scholar, 6Lucas M. Arnold A. Sommerfiled A. Trevenen M. Braconnier L. et al.Antibiotic allergy labels in children are associated with adverse clinical outcomes.J Allergy Clin Immunol Pract. 2018; 7: 975-982Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar These costs include longer hospitalizations for both children and adults, higher rates of infections with drug-resistant organisms including Clostridium difficile, methicillin-resistant S aureus, and vancomycin-resistant enterococcus, and the use of more expensive antibiotics.5Macy E. Contreras R. Healthcare utilization and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study.J Allergy Clin Immunol. 2014; 133: 790-796Abstract Full Text Full Text PDF PubMed Scopus (404) Google Scholar, 6Lucas M. Arnold A. Sommerfiled A. Trevenen M. Braconnier L. et al.Antibiotic allergy labels in children are associated with adverse clinical outcomes.J Allergy Clin Immunol Pract. 2018; 7: 975-982Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar In a study of adult patients at Kaiser, the costs of increased length of stay for hospitalized patients with penicillin allergies vs those without was about 9.5 times the amount an allergy evaluation would cost; in absolute numbers, this cost was estimated to be about $64 million in increased costs over 3 years in the population studied.5Macy E. Contreras R. Healthcare utilization and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study.J Allergy Clin Immunol. 2014; 133: 790-796Abstract Full Text Full Text PDF PubMed Scopus (404) Google Scholar With these estimates in mind, the American Academy of Allergy Asthma and Immunology recommends routine evaluation of penicillin allergies, and American and Canadian Choosing Wisely initiatives encourage this strategy as well.7Lang D.M. Castells M.C. Khan D. Macy E.M. Murphy A.W. Penicillin allergy testing should be performed routinely in patients with self-reported penicillin allergy.J Allergy Clin Immunol Pract. 2016; 5: 333-334Google Scholar, 8American Academy of Allergy, Asthma & ImmunologyChoosing wisely: ten things physicians and patients should question.www.choosingwisely.org/clinician-lists/american-academy-allergy-asthma-immunlogy-non-beta-lactam-antibiotics-penicillin-allergyGoogle Scholar, 9Choosing Wisely CanadaFive things physicians and patients should question.https://choosingwiselycanada.org/infectious-diseaseGoogle Scholar A Grand Rounds article reviewed the literature showing that most children labeled as allergic to penicillin are not actually allergic and outlined the many reasons to unlabel them.10Abrams E.M. Atkinson A.R. Wong T. Ben-Shoshan M. The importance of delabeling β-lactam allergy in children.J Pediatr. 2019; 204: 291-297Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar More than 90% of children labeled as allergic who are tested are able to pass a challenge to amoxicillin, with no immunologically mediated reactions (no hives, anaphylaxis, or delayed rashes).11Mill C. Primeau M.N. Medoff E. Lejtenyi C. O'Keefe A. Netchiporouk E. et al.Assessing the diagnostic properties of a graded oral provocation challenge for the diagnosis of immediate and nonimmediate reactions to amoxicillin in children.JAMA Pediatr. 2016; 170: e160033Crossref PubMed Scopus (158) Google Scholar However, not all patients need to be sent to an allergist. The Figure provides a recommended framework for distinguishing who needs referral. Patients with “side effects” to penicillin can safely take the medication again at home, getting the green light as shown in the Figure. A helpful framework from the classic 1977 schema from Rawlins and Thomson subdivides adverse drug reactions into type A reactions, which are predictable, common, and related to the mechanism of action of the drug (ie, diarrhea with antibiotics), and type B reactions, which are unpredictable and idiosyncratic, and include the different types of drug allergy.12Rawlins M.D. Thompson J.W. Pathogenesis of adverse drug reactions.in: Davies D.M. Textbook of adverse drug reactions. Oxford University Press, Oxford1977: 10Google Scholar, 13Rawlins M.D. Clinical pharmacology: adverse reactions to drugs.BMJ. 1981; 282: 974-976Crossref PubMed Scopus (88) Google Scholar Drug allergies have distinct features that are usually distinguishable by history of rash and other associated symptoms that depend on the severity and mechanism, reviewed here. Using this schema, the boys in the first case could have received amoxicillin without an allergy evaluation. Because the differences are often confusing, it behooves all pediatricians to reinforce to patients the difference between side effects and immunologically mediated drug allergies when time allows. The published toolkit in the Journal of the American Medical Association also suggests that patients with “intolerance,” noncutaneous, or benign somatic complaints, such as headache, that are clearly not allergic may undergo an oral challenge to penicillin without skin testing; all of these fall in the green light category in the Figure.14Shenoy E.S. Macy E. Rowe T. Blumenthal K. et al.Evaluation and management of penicillin allergy: a review.JAMA. 2019; 321: 188-199Crossref PubMed Scopus (154) Google Scholar This strategy can also be used if the family is avoiding amoxicillin only owing to a relative's allergy. Although there is evidence supporting each of these recommendations, it remains to be seen how successfully pediatricians can systematically apply this approach to delabeling penicillin allergies. Another tactic is to prevent the relabeling of penicillin allergies, which can be tenacious and difficult to eliminate. Studies have shown that, even after patients pass an oral challenge in an allergist's office, the allergies frequently pop up again in the electronic medical record. In 1 study of long-term follow-up after penicillin delabeling, 335 of 639 patients (51%) still had the penicillin allergy listed in their chart after a successful challenge.15Lachover-Roth I. Sharon S. Rosman Y. Meir-Shafrir K. Confino-Cohen R. Long-term follow-up after penicillin allergy delabeling in ambulatory patients.J Allergy Clin Immunol. 2019; 135: 956-963Google Scholar This lack of change may occur because patients re-endorse the allergy or do not understand the significance of challenge procedure. Medical staff may want to re-enter the allergy just to be safe. In addition, clarity is lacking in how these allergies are recorded in the first place. In EPIC, the most commonly used electronic medical record in the US, drug allergies are listed alongside intolerances, and can be mixed in with food and environmental allergies (ie, dust mite or pollen sensitization). It is no wonder that the lines between side effects and allergies blur. Pediatric staff can be alerted to this issue and help to reinforce the understanding that once the allergy has been removed from the record it does not need to be relisted unless there are new allergic symptoms. Penicillin first came into widespread use in the 1940s, and the first case of anaphylaxis was reported in 1946, with the first death in 1949.16O'Donovan W.J. Klorfajn I. Sensitivity to penicillin: anaphylaxis and desensitization.Lancet. 1946; 2: 444Abstract PubMed Scopus (28) Google Scholar, 17Waldbott II, G. Anaphylactic death from penicillin.JAMA. 1949; 139: 526Crossref Scopus (10) Google Scholar In a case series of 9 adult patients reported by Feinberg et al in 1953, deaths were after either intramuscular injection or direct inhalation.18Feinberg S.M. Feinberg A.R. Moran C.E. Penicillin anaphylaxis, nonfatal and fatal reactions.J Am Med Assoc. 1953; 152: 114-119Crossref PubMed Scopus (5) Google Scholar Although the authors described anecdotal reactions after oral ingestion of penicillin, they do not describe these cases and call for better reporting of reactions. Idsoe et al reported reaction rates among larger group of patients, including summary surveys from several diverse countries.19Idsoe O. Guthe T. Willcox R.R. de Weck A.L. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock.Bull World Health Organ. 1968; 38: 159-188PubMed Google Scholar Of all the data presented, the paper concludes that the most reliable is a physician survey including 200 000 Swiss patients, with an anaphylaxis rate of 0.04% and a fatality rate of 0.002%, or 1 in 50 000. Citing these references, review articles from the 1980s through the 2000s describe penicillin as one of the most important causes of fatal anaphylaxis; 75% of fatal anaphylaxis, estimated to be at least 500 cases per year.20Weiss M.E. Adkinson N.F. Immediate hypersensitivity reactions to penicillin and related antibiotics.Clin Allergy. 1988; 18: 515-540Crossref PubMed Scopus (307) Google Scholar, 21Neugut A.I. Ghatak A.T. Miller R.L. Anaphylaxis in the United States: an investigation into its epidemiology.Arch Intern Med. 2001; 16: 15-21Google Scholar The source of these figures is difficult to trace and seem to be based on estimates from the earlier studies. Larger, more recent studies have been less alarming from a pediatric perspective. A study of more than 500 000 MedWatch adverse event reports to the US Food and Drug Administration over roughly 3 years included 6 antibiotics in the list of top 17 most common drugs associated with adverse events; amoxicillin and penicillin did not make the list, which did include azithromycin, fluconazole, ceftriaxone, cefaclor, cefoperazone, erythromycin, and vancomycin.22Moore T.J. Weiss S.R. Kaplan S. Blaisdell C.J. Reported adverse drug events in infants and children under 2 years of age.Pediatrics. 2002; 110: e53Crossref PubMed Scopus (103) Google Scholar Jerschow et al examined fatal anaphylaxis in the US between 1999 and 2010 using International Classification of Disease, 10th edition, data from death certificates collected by the National Center for Health Statistics.23Jerschow E. Lin R.Y. Scaperotti M.M. McGinn A.P. Fatal anaphylaxis in the United States, 1999-2010: temporal patterns and demographic associations.J Allergy Clin Immunol. 2014; 134: 1318-1328Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar Drug reactions accounted for the largest percentage of deaths (66%), but none of the 1446 patients were younger than 47 years old. Antibiotics as a class accounted for 41% of these fatalities. More recent data have shown that although rates of all-cause anaphylaxis in the US, UK, and Australia are increasing, there is not an increase in fatalities and no association with penicillin allergies in young children.24Ma L. Danoff T.M. Borish L. Case fatality and population mortality associated with anaphylaxis in the United States.J Allergy Clin Immunol. 2014; 133: 1075-1083Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar, 25Turner P.J. Gowland M.H. Sharma V. Ierodiakonou D. Haprer N. Garcez T. et al.Increase in anaphylaxis-related hospitalizations but in no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992-2012.J Allergy Clin Immunol. 2015; 135: 956-963Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar, 26Liew W.K. Williamson E. Tang M.L. Anaphylaxis fatalities and admissions in Australia.J Allergy Clin Immunol. 2009; 123: 434-442Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar In fact, there were no reported deaths from any cases of medication anaphylaxis in general in children under age 9 in either the UK or Australian national database studies.25Turner P.J. Gowland M.H. Sharma V. Ierodiakonou D. Haprer N. Garcez T. et al.Increase in anaphylaxis-related hospitalizations but in no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992-2012.J Allergy Clin Immunol. 2015; 135: 956-963Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar, 26Liew W.K. Williamson E. Tang M.L. Anaphylaxis fatalities and admissions in Australia.J Allergy Clin Immunol. 2009; 123: 434-442Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar Similar to the US, in both the UK and Australia, patients over 60 years of age are at highest risk for drug-induced anaphylaxis; the Australian deaths related to penicillin were specifically reported, and were only patients between 60 and 74 years of age. These epidemiologic studies suggest that fatal, immediate-type hypersensitivity reactions, ie, death from anaphylaxis, to penicillin is exceedingly rare in children. Therefore, pediatricians in many health care settings should feel even more comfortable giving penicillin in the setting of the concerns to the left of the algorithm. In addition, families such as those in the first case should be encouraged to be evaluated by an allergist, because there is little evidence for significant immediate reactions in the literature. Any child with a rash should be referred to an allergist (Figure). This step is recommended because a rash is a consistent feature of both immediate and delayed drug hypersensitivities, and allergists have trained in elucidating these details and determining if an oral challenge is contraindicated. The second case represents a history commonly seen in the allergy clinic for penicillin allergy, in which there is no evidence of an immediate reaction (no hives, angioedema, or other features of anaphylaxis) and no features of dangerous delayed reactions as reviewed elsewhere in this article. Skin testing has traditionally been the first step in any penicillin allergy evaluation. The procedure was developed in the 1960s by Levine et al at New York University as a way to objectively evaluate penicillin reactions.27Levine B.B. Redmond A.P. Voss H. Zolov D.M. Prediction of penicillin allergy by immunological tests.Ann N Y Acad Sci. 1967; 145: 298-309Crossref PubMed Scopus (23) Google Scholar Penicillin skin testing has a sensitivity of more than 90% for immediate IgE-mediated hypersensitivity reactions, with a specificity in adults of about 50%.2Parmer J.S. Nasser S. Antibiotic allergy in cystic fibrosis.Thorax. 2005; 60: 517-520Google Scholar Skin testing is not validated for nonimmediate, non–IgE-mediated drug reactions. This, coupled with a graded oral challenge of 10% followed by 90% of the dose and an observation period, is the accepted gold standard for evaluation of immediate penicillin reactions. In young children, this gold standard test can be very difficult to achieve. This is understandable, because there are real reasons to be scared of penicillin skin testing! The standard protocol involves skin prick testing with saline, histamine, ampicillin (a surrogate amino-penicillin for amoxicillin because this agent cannot be used to skin test), penicillin, and the protein conjugate benzylpenicilloyl polylysine (also known as “pre-pen,” the “major determinant” the antigen most commonly responsible for IgE-mediated reactions). Then come intradermal injections with saline, ampicillin, penicillin, and 1 or 2 with pre-pen. That adds up to 4 intradermal injections—the same procedure as 4 intradermal tuberculin skin tests. Very few toddlers or school-aged children tolerate this regimen without pain and distress. Data from Kaiser have already shown decreasing rates of positive skin tests, with a decrease from more than 10% to less than 5% over a 13-year period.28Macy E. Schatz M. Lin C.K. Poon K.-Y. The falling rate of positive penicillin skin tests from 1995 to 2007.Perm J. 2009; 13: 12-18Crossref PubMed Google Scholar Studies have suggested that skin testing may not even be necessary for the majority of outpatients with a history of cutaneous reactions.11Mill C. Primeau M.N. Medoff E. Lejtenyi C. O'Keefe A. Netchiporouk E. et al.Assessing the diagnostic properties of a graded oral provocation challenge for the diagnosis of immediate and nonimmediate reactions to amoxicillin in children.JAMA Pediatr. 2016; 170: e160033Crossref PubMed Scopus (158) Google Scholar, 29Collins C.A. Choe D. Mochizuki D. Cannavino C. Evaluating penicillin allergies in children using a standard EMR-based questionnaire.Ann Allergy Asthma Immunol. March 13, 2019; (, in press)Google Scholar, 30Tucker M.H. Lomas C.M. Ramchandar N. Waldram J.D. Amoxicillin challenge without penicillin skin testing in evaluation of penicillin allergy in a cohort of Marine recruits.J Allergy Clin Immunol Pract. 2017; 5: 813-815Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 31Labrosse R. Paradis L. Lacombe J. et al.Efficacy and safety of 5-day challenge for the evaluation of nonsevere amoxicillin allergy in children.J Allergy Clin Immunol Pract. 2018; 6: 1673-1680Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 32Iammatteo M. Alvarez A. Ferastraoaru D. et al.Safety and outcomes of oral graded challenges to amoxicillin without prior skin testing.J Allergy Clin Immunol Pract. 2019; 7: 236-243Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar One of the first studies to demonstrate this outcome was in Marine recruits in San Diego.31Labrosse R. Paradis L. Lacombe J. et al.Efficacy and safety of 5-day challenge for the evaluation of nonsevere amoxicillin allergy in children.J Allergy Clin Immunol Pract. 2018; 6: 1673-1680Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar Recruits are given an injection of penicillin G benzathine on enlistment as a prophylaxis against streptococcal infections. After performing 74 consecutively negative skin tests in penicillin-allergic patients, the allergists decided to skip this step and pursue direct oral challenge. Patients were excluded if they had a history of serious cutaneous reactions (urticarial/angioedema) or hepatitis, nephritis, or hemolytic anemia. Three hundred twenty-eight recruits had a direct oral challenge and 5 had mild acute reactions, one of which included globus. All of these patients were treated with antihistamines and an epinephrine injection to avoid reaction progression. Marines are a tough bunch, but can we safely translate these results to children? This translation has actually been done in several studies with promising results. The largest, a study of 801 children including patients with history of immediate reactions to penicillin and hives, confirmed the safety of direct oral challenges without antecedent skin testing.11Mill C. Primeau M.N. Medoff E. Lejtenyi C. O'Keefe A. Netchiporouk E. et al.Assessing the diagnostic properties of a graded oral provocation challenge for the diagnosis of immediate and nonimmediate reactions to amoxicillin in children.JAMA Pediatr. 2016; 170: e160033Crossref PubMed Scopus (158) Google Scholar Seventeen children (2.1%) had mild immediate reactions and 31 children (3.8%) had nonimmediate reactions. A prior history of a reaction within 5 minutes did correlate with the likelihood of having an immediate reaction. The authors performed skin testing on the 17 children who had immediate reactions, and only 1 child had a positive skin test. Including skin testing in the protocol approximately doubled the cost of the evaluation; the conclusion was that even with mild reactions the expensive and painful skin testing procedure may not be necessary. In this author's practice at Rady Children's Hospital San Diego, there is skin testing available for patients who have a history consistent with immediate-type reactions (rash on the first day of medication, or who have raised and mobile rash consistent with hives); we have been able to proceed to oral challenges without skin testing for most patients and would recommend this option for the second patient.29Collins C.A. Choe D. Mochizuki D. Cannavino C. Evaluating penicillin allergies in children using a standard EMR-based questionnaire.Ann Allergy Asthma Immunol. March 13, 2019; (, in press)Google Scholar If skin testing is not needed, it might be possible to consider doing oral challenges for patients with a history of rash outside of an allergist's office, say in a pediatrician's office or in the emergency room. However, oral challenges have traditionally been the purview of allergists who have the staff on hand trained to deal with allergic reactions; there are not as yet structures in place to allow these allergies to be evaluated in the most primary care clinics. Emergency room physicians have taken the lead in several studies in offering further evaluation of allergies during emergency room visits for other reasons, either testing for the allergies with skin testing for adults or by offering testing at a later date.33Raja A.S. Lindsell C.J. Bernstein J.A. Codispoti C.D. Moellman J.J. The use of penicillin skin testing to assess the prevalence of penicillin allergy in an emergency room setting.Ann Emerg Med. 2009; 54: 72-77Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 34Vyles D. Adams J. Chiu A. Simpson P. Nimmer M. Brousseau D.C. Allergy testing in children with low-risk penicillin allergy symptoms.Pediatrics. 2017; 140Crossref PubMed Scopus (53) Google Scholar The feasibility of completing oral challenges in other practice settings is unproven; thus, any patient with a rash should be seen by an allergist who has the time and space to supervise oral challenges, and expertise in identifying concerning features that would be contraindications to retesting the antibiotic, as discussed here. A subtle but significant point of confusion is when in penicillin allergies should the referral be placed. How close to having a reaction is it worth testing for the allergy? Our allergy guidance documents state that the rates of allergies decrease over time; a commonly cited statistic is that 80% have cleared the allergy in 10 years.1Solensky R. Khan D.A. Bernstein I.L. et al.Joint Task Force on Practice ParametersAmerican Academy of Allergy, Asthma and ImmunologyAmerican College of Allergy, Asthma and ImmunologyJoint Council of Allergy, Asthma and ImmunologyDrug allergy: an updated practice parameter.Ann Allergy Asthma Immunol. 2010; 105: 259-273Abstract Full Text Full Text PDF PubMed Scopus (589) Google Scholar However, children with cutaneous reactions can be evaluated and tolerate penicillins within weeks or months of the initial rash.11Mill C. Primeau M.N. Medoff E. Lejtenyi C. O'Keefe A. Netchiporouk E. et al.Assessing the diagnostic properties of a graded oral provocation challenge for the diagnosis of immediate and nonimmediate reactions to amoxicillin in children.JAMA Pediatr. 2016; 170: e160033Crossref PubMed Scopus (158) Google Scholar It would be reasonable to refer any patient within a few months of the initial reaction, once their rash has resolved. Despite the data indicating that most penicillin allergies are not persistent or dangerous, allergists and many pediatricians have seen life-threatening drug reactions in children; no physician can forget a case of desquamation with Stevens-Johnson syndrome (SJS) or renal injury with a drug-induced hypersensitivity syndrome (also known as drug reaction with eosinophilia with systemic symptoms). These drug reactions are part of a larger group known as severe cutaneous adverse reactions (SCARs), which also include acute generalized exanthemous pustulosis, which is characterized by a pustular rash and organ involvement.35Duong T.A. Valeyrie-Allanore L. Wolkenstien P. Chosidow O. Severe cutaneous adverse reactions to drugs.Lancet. 2017; 390: 1996-2001Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar These types of drug reactions are strict contraindications to retrial of the offending medication, because there is a high fatality rate with the initial reaction (≤40% with SJS/toxic epidermal necrolysis, 10% for drug ras" @default.
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• W2956044946 date "2019-09-01" @default.
• W2956044946 modified "2023-09-26" @default.
• W2956044946 title "The Low Risks and High Rewards of Penicillin Allergy Delabeling: An Algorithm to Expedite the Evaluation" @default.
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• W2956044946 doi "https://doi.org/10.1016/j.jpeds.2019.05.060" @default.
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