Drug allergy de-labelling with a direct oral challenge in outpatient hospital visits

Drug allergy de-labelling with a direct oral challenge in outpatient hospital visits | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Drug allergy de-labelling with a direct oral challenge in outpatient hospital visits Nadir Sekkai, Magalie Coco-Viloin, Mathilde Calmels, Laurent Guilleminault This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8852874/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract Although oral direct challenge has been adopted by numerous clinicians around the world in a context of drug hypersensitivity, drug allergy de-labelling remains largely confined to hospital-based care and mostly for penicillins In this study, we aim to perform direct oral drug challenge (DODC) in patients with low-risk allergy to drugs (not only penicillin) in outpatient visits. We conducted a prospective single-centre study from May 2022 to January 2024. Inclusion criteria were age ≥14 years and a label of drug allergy with an initial reaction compatible with an allergic reaction. Exclusion criteria were severe anaphylaxis or severe cutaneous adverse drug reactions or prior skin tests to the suspected drug. The culprit drug was given as a standard single dose in an outpatient hospital visit. In total, 304 patients were included. Penicillins were the most frequent culprit drugs with 228 (75%) patients. The other drugs involved in allergy labelling were as follows: nonsteroidal anti-inflammatory drugs (NSAIDs) in 31 (10.2%) patients, cephalosporins in 10 (3.3%) patients, other antibiotics in 15 (4.9%) patients, analgesics in 7 (2.3%) patients and corticosteroids in 4 (1.3%) patients. Nine (3.0%) patients had a reaction with other drugs. Among the whole cohort, 295 (97.0%) had no reaction during DODC. Ten patients presented a mild reaction including three patients with an immediate reaction and six with a delayed reaction. In conclusion, allergy de-labelling to all drugs in patients with low-risk allergies can be safely conducted in outpatient visits. drug allergy challenge Main Text Drug allergy labelling is a considerable public health problem in clinical practice[1]. A recent study estimated that 11.3% of households report drug hypersensitivity in the US[2]. However, it is well established that a label of drug allergy is largely inaccurate in most patients[3]. Unfortunately, the assignment of a drug allergy label leads to unnecessary treatment with a high morbidity and mortality[4]. A de-labelling procedure is highly valuable for patients by reducing the use of inadequate drugs. Recently, oral direct challenge has emerged in low risk allergy patients with a very good safety profile[5]. Although oral direct challenge has been adopted by numerous clinicians around the world, drug allergy de-labelling remains largely confined to hospital-based care and mostly for penicillins. In this study, we aim to perform direct oral challenge in patients with low-risk allergy to drugs (not only penicillin) in outpatient visits. We conducted a prospective single-centre study from May 2022 to January 2024. Inclusion criteria were age ≥14 years at the time of investigation and a label of drug allergy with an initial reaction compatible with an allergic reaction (cutaneous, respiratory or digestive symptoms). Exclusion criteria were a reaction compatible with severe anaphylaxis or severe cutaneous adverse drug reactions (toxic epidermal necrolysis, Stevens–Johnson syndrome, DRESS syndrome), uncontrolled asthma at the time of testing, ongoing pregnancy, active infection or prior skin tests to the suspected drug. Patients reporting drug allergy with a clinical history suggesting adverse events rather than a true allergy—such as headache or dry mouth—were not included. Those patients were de-labelled with no oral challenge. Discontinuation of antihistamines, corticosteroids, and beta-blockers was recommended but not mandatory for the direct oral drug challenge (DODC). Written consent was obtained from each patient for adults and from the legal guardian for teenagers. This study was conducted in accordance with French ethics requirements (register number: RnIPH 2024-68) and the French Data Protection Authority (CNIL number: 2206723 v 0). DODC was performed as follows. The culprit drug was given in an outpatient hospital visit. The drug dose corresponded to a standard single dose, as used under real-life conditions. Vital signs (blood pressure, heart rate, oxygen saturation) were measured before the test. Clinical monitoring was carried out for one hour in the consultation waiting area. In the case of an immediate reaction (≤1 hour), vital signs were measured and appropriate treatment was administered. In the case of a delayed reaction (>1 hour) occurring at home, patients were instructed to contact the department by e-mail and, if possible, to provide photographs in order to characterise the type of reaction. Quantitative variables were presented as means and standard deviations when normally distributed. In the absence of a normal distribution, data were expressed as medians and interquartile ranges. Qualitative variables were presented as numbers and percentages. In total, 304 patients were included, composed of 222 (73.5%) females with a mean age of 46.3 ± 17.6 (Table 1). Penicillins were the most frequent culprit drugs with 228 (75%) patients. The other drugs involved in allergy labelling were as follows: nonsteroidal anti-inflammatory drugs (NSAIDs) in 31 (10.2%) patients, cephalosporins in 10 (3.3%) patients, other antibiotics in 15 (4.9%) patients, analgesics in 7 (2.3%) patients and corticosteroids in 4 (1.3%) patients. Nine (3.0%) patients had a reaction with other drugs (Table 1). Regarding the details of the initial reaction, most of the patients (n=169, 55.6%) had experienced a reaction more than 10 years prior to DODC (Table 1). In 44 patients (14.4%), the time of the initial reaction was unknown. Most of the patients (n=163, 53.6%) were unable to provide details about the initial reaction. Among the whole cohort, 295 (97.0%) had no reaction during the DODC. Three patients presented an immediate reaction with only cutaneous manifestations in all cases (Table 2). One patient also reported nausea without vomiting. Among the six patients who experienced a delayed reaction, five showed cutaneous reactions. One patient experienced nausea and vomiting with no skin symptoms. All of the reactions were considered as mild. Among the 10 patients who experienced a reaction, six received a single dose of antihistamines. No patient required epinephrine injection or hospitalisation. Drug allergy labelling has a detrimental effect on patients’ healthcare. The procedures that lead to drug allergy de-labelling are crucial for healthcare improvement and a reduction of inappropriate drug use. Up to now, drug allergy de-labelling via direct oral challenge has been widely performed for penicillins in children due to their massive use in childhood[6]. However, it is now well established that direct oral challenge is also safe in adults for penicillins[7]. Allergy de-labelling for other drugs than penicillins has been little studied. Safe cephalosporin allergy de-labelling has recently emerged[8]. However, large-scale drug allergy de-labelling is necessary due to the risk of inadequate use of drugs, particularly in critical situations. For the first time, we show that direct oral challenge to drugs other than penicillins is safe with the opportunity for patients to have access to effective drugs such as pain-killers or NSAIDs. Our study also introduces the concept of large-scale drug allergy de-labelling in outpatient visits. Given the high number of patients with drug allergy labels, it is imperative to find the best way to de-label patients. The situation of the healthcare system in Europe and also the rest of the world is deteriorating due to the increased number of patients and the shortage of healthcare professionals, particularly in hospitals[9]. A direct drug challenge in an outpatient visit ensures a larger number of patients with drug allergy de-labelling and a reduction in healthcare professionals involved in care. For these reasons, our study provides data that will change the way in which drug allergy labelling is addressed. Our study has several limitations. We did not use a validated score such as PEN-FAST because there is no validated score for drugs other than penicillins[7]. Moreover, no placebo arms were used for our study. In conclusion, allergy de-labelling to all drugs in patients with low-risk allergies can be safely conducted in outpatient visits. Declarations Disclosure of interest: Prof Guilleminault reports grants, personal fees and/or non-financial support from Astrazeneca, GSK, Novartis, Chiesi, Sanofi, Stallergenes, ALK, Bayer and MSD outside from the submitted work. Author Contribution NS: Conceptualisation; Investigation; Methodology; Project administration; Validation; Visualisation; Writing – original draft; Writing – review & editing; Data curation ResourcesMCV and MC: Investigation; Methodology; Project administration; Validation; Visualisation; Writing – review & editingLG: Conceptualisation; Formal analysis; Investigation; Methodology; Project administration; Supervision; Validation; Visualisation; Writing – original draft; Writing – review & editing; Data curation Resources Data Availability The data will be available on request. References Doña I, Torres MJ, Celik G, Phillips E, Tanno LK, Castells M. Changing patterns in the epidemiology of drug allergy. Allergy. 2024;79(3):613–28. Kottapalli A, Warren CM, Nimmagadda SR, Bartell TR, Gupta RS. The distribution and determinants of physician-diagnosed drug allergy in a large, nationally representative sample of US children and adults. J Allergy Clin Immunol Pract. 2024;12(2):515–8. Stone CA Jr., Trubiano J, Coleman DT, Rukasin CRF, Phillips EJ. The challenge of de-labeling penicillin allergy. Allergy. 2020;75(2):273–88. 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(3): 790–6. Castells M, Khan DA, Phillips EJ. Penicillin Allergy. N Engl J Med. 2019;381(24):2338–51. Providencia R, Aali G, Zhu F, Leas BF, Orrell R, Ahmad M, Bray JJH, Pelone F, Nass P, Marijon E, Cassandra M, Celermajer DS, Shokraneh F. Penicillin Allergy Testing and Delabeling for Patients Who Are Prescribed Penicillin: A Systematic Review for a World Health Organization Guideline. Clin Rev Allergy Immunol. 2024;66(2):223–40. Copaescu AM, Vogrin S, James F, Chua KYL, Rose MT, De Luca J, Waldron J, Awad A, Godsell J, Mitri E, Lambros B, Douglas A, Youcef Khoudja R, Isabwe GAC, Genest G, Fein M, Radojicic C, Collier A, Lugar P, Stone C, Ben-Shoshan M, Turner NA, Holmes NE, Phillips EJ, Trubiano JA. Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial. JAMA Intern Med. 2023;183(9):944–52. Moraczewski J, Lee R, Koo G, Krantz MS, Allocco C, Phillips EJ, Stone CA. Jr. Direct oral challenges safely reduce the burden of low-risk cephalosporin allergy labels. J Allergy Clin Immunol Pract. 2025;13(9):2522–e25252521. Armitage R. The case for introducing a minimum NHS service requirement for UK-trained doctors. J Med Ethics 2025. Tables Table 1. Characteristics of the total population. * Data Total population n=304 Age 46.3 ± 17.6 Female 222 (73.5%) Atopy 55 (18.2%) Mastocytosis 1 (0.3%) Time since the initial reaction 10 years Unknown 49 (16.1%) 27 (8.8%) 15 (4.9%) 169 (55.6%) 44 (14.4%) Time between drug intake and symptoms for the initial reaction Immediate Non-immediate Unknown 27 (8.9%) 114 (37.5 %) 163 (53.6%) Culprit drugs Penicillin NSAIDs Other antibiotics Cephalosporins Others* Analgesics (excluding NSAIDs) Corticosteroids 228 (75.0%) 31 (10.2%) 15 (4.9%) 10 (3.3% 9 (3.0% 7 (2.3%) 4 (1.3%) *others : Pylera®, Fyremadel, Macrogol, Furosemide, Pantoprazole, Nitrofurantoine, Hydrochlorothiazide, Enoxaparine, Metoclopramide. Table 2: details of patients with positive oral drug challenge Sex Female Female Female Female Female Female Female Male Female Age (years) 61 43 41 70 60 80 30 23 48 Date of onset > 10 years > 10 years > 10 years < 1 year 1-5 years 1-5 years 10 years > 10 years Initial reaction delay Immediate Unknown Unknown Immediate Delayed Delayed Delayed Delayed Delayed Initial reaction Facial erythema Skin rash Angioedema Generalised erythema and facial angiodema Generalised urticaria Truncal urticaria Vomiting Urticaria Unknown Suspected drug Penicillin Aspirin Penicillin Cotrimoxazole Pylera (Bismuth, metronidazole, and tetracycline) Amoxicillin Ketoprofen Amoxicillin–clavulanate Penicillin Drug oral challenge Amoxicillin Aspirin Amoxicillin–clavulanate Cotrimoxazole Pylera (Bismuth, metronidazole, and tetracycline) Amoxicillin Ketoprofen Amoxicillin–clavulanate Amoxicillin Onset of reaction following oral drug challenge 30 minutes 50 minutes 30 minutes 6 hours 24 hours 48 hours 6 hours 24 hours 24 hours Details of the reaction Facial erythema and nausea Urticarial papules on the abdomen and back Urticaria on the trunk, back, and legs Pruritus and erythema of the trunk, face, and back Urticaria of the lower limbs Generalized urticaria Nausea, abdominal pain, and two episodes of vomiting Maculopapular rash and fever Generalized urticaria Treatment administred H1-antihistamine H1-antihistamine H1-antihistamine H1-antihistamine 0 0 0 H1-antihistamine H1-antihistamine Hospitalisation 0 0 0 0 0 0 0 0 0 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 18 Mar, 2026 Reviews received at journal 18 Mar, 2026 Reviews received at journal 27 Feb, 2026 Reviewers agreed at journal 25 Feb, 2026 Reviewers agreed at journal 23 Feb, 2026 Reviewers invited by journal 23 Feb, 2026 Editor assigned by journal 18 Feb, 2026 Submission checks completed at journal 18 Feb, 2026 First submitted to journal 11 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8852874","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":597147184,"identity":"530855d2-cc0c-4ea7-b7d9-9ad990d26961","order_by":0,"name":"Nadir Sekkai","email":"","orcid":"","institution":"CHU de Toulouse","correspondingAuthor":false,"prefix":"","firstName":"Nadir","middleName":"","lastName":"Sekkai","suffix":""},{"id":597147186,"identity":"22171580-c0cd-406a-a526-098d63972026","order_by":1,"name":"Magalie Coco-Viloin","email":"","orcid":"","institution":"CHU de Toulouse","correspondingAuthor":false,"prefix":"","firstName":"Magalie","middleName":"","lastName":"Coco-Viloin","suffix":""},{"id":597147187,"identity":"0eff77dc-ef89-4b68-8efa-e394111f5a05","order_by":2,"name":"Mathilde Calmels","email":"","orcid":"","institution":"CHU de Toulouse","correspondingAuthor":false,"prefix":"","firstName":"Mathilde","middleName":"","lastName":"Calmels","suffix":""},{"id":597147188,"identity":"028d4d82-0660-4f39-872b-2bba06a7fb34","order_by":3,"name":"Laurent Guilleminault","email":"data:image/png;base64,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","orcid":"","institution":"CHU de Toulouse","correspondingAuthor":true,"prefix":"","firstName":"Laurent","middleName":"","lastName":"Guilleminault","suffix":""}],"badges":[],"createdAt":"2026-02-11 14:38:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8852874/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8852874/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104397944,"identity":"6054b687-0299-450a-8b39-f436e14289ab","added_by":"auto","created_at":"2026-03-11 11:59:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":449181,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8852874/v1/8e4604e9-b4a1-4fbe-9159-cba48e657d63.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Drug allergy de-labelling with a direct oral challenge in outpatient hospital visits","fulltext":[{"header":"Main Text","content":"\u003cp\u003eDrug allergy labelling is a considerable public health problem in clinical practice[1]. A recent study estimated that 11.3% of households report drug hypersensitivity in the US[2]. However, it is well established that a label of drug allergy is largely inaccurate in most patients[3]. Unfortunately, the assignment of a drug allergy label leads to unnecessary treatment with a high morbidity and mortality[4]. A de-labelling procedure is highly valuable for patients by reducing the use of inadequate drugs. Recently, oral direct challenge has emerged in low risk allergy patients with a very good safety profile[5]. Although oral direct challenge has been adopted by numerous clinicians around the world, drug allergy de-labelling remains largely confined to hospital-based care and mostly for penicillins.\u003c/p\u003e\n\u003cp\u003eIn this study, we aim to perform direct oral challenge in patients with low-risk allergy to drugs (not only penicillin) in outpatient visits.\u003c/p\u003e\n\u003cp\u003eWe conducted a prospective single-centre study from May 2022 to January 2024. Inclusion criteria were age ≥14 years at the time of investigation and a label of drug allergy with an initial reaction compatible with an allergic reaction (cutaneous, respiratory or digestive symptoms). Exclusion criteria were a reaction compatible with severe anaphylaxis or severe cutaneous adverse drug reactions (toxic epidermal necrolysis, Stevens–Johnson syndrome, DRESS syndrome), uncontrolled asthma at the time of testing, ongoing pregnancy, active infection or prior skin tests to the suspected drug. Patients reporting drug allergy with a clinical history suggesting adverse events rather than a true allergy—such as headache or dry mouth—were not included. Those patients were de-labelled with no oral challenge. Discontinuation of antihistamines, corticosteroids, and beta-blockers was recommended but not mandatory for the direct oral drug challenge (DODC). Written consent was obtained from each patient for adults and from the legal guardian for teenagers. This study was conducted in accordance with French ethics requirements (register number: RnIPH 2024-68) and the French Data Protection Authority (CNIL number: 2206723 v 0).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDODC was performed as follows.\u0026nbsp;\u003c/strong\u003eThe culprit drug was given in an outpatient hospital visit. The drug dose corresponded to a standard single dose, as used under real-life conditions. Vital signs (blood pressure, heart rate, oxygen saturation) were measured before the test. Clinical monitoring was carried out for one hour in the consultation waiting area. In the case of an immediate reaction (≤1 hour), vital signs were measured and appropriate treatment was administered. In the case of a delayed reaction (\u0026gt;1 hour) occurring at home, patients were instructed to contact the department by e-mail and, if possible, to provide photographs in order to characterise the type of reaction.\u003c/p\u003e\n\u003cp\u003eQuantitative variables were presented as means and standard deviations when normally distributed. In the absence of a normal distribution, data were expressed as medians and interquartile ranges. Qualitative variables were presented as numbers and percentages.\u003c/p\u003e\n\u003cp\u003eIn total, 304 patients were included, composed of 222 (73.5%) females with a mean age of 46.3 ± 17.6 (Table 1). Penicillins were the most frequent culprit drugs with 228 (75%) patients. The other drugs involved in allergy labelling were as follows: nonsteroidal anti-inflammatory drugs (NSAIDs) in 31 (10.2%) patients, cephalosporins in 10 (3.3%) patients, other antibiotics in 15 (4.9%) patients, analgesics in 7 (2.3%) patients and corticosteroids in 4 (1.3%) patients. Nine (3.0%) patients had a reaction with other drugs (Table 1). Regarding the details of the initial reaction, most of the patients (n=169, 55.6%) had experienced a reaction more than 10 years prior to DODC (Table 1). In 44 patients (14.4%), the time of the initial reaction was unknown. Most of the patients (n=163, 53.6%) were unable to provide details about the initial reaction.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong the whole cohort, 295 (97.0%) had no reaction during the DODC. Three patients presented an immediate reaction with only cutaneous manifestations in all cases (Table 2). One patient also reported nausea without vomiting. Among the six patients who experienced a delayed reaction, five showed cutaneous reactions. One patient experienced nausea and vomiting with no skin symptoms. All of the reactions were considered as mild. Among the 10 patients who experienced a reaction, six received a single dose of antihistamines. No patient required epinephrine injection or hospitalisation.\u003c/p\u003e\n\u003cp\u003eDrug allergy labelling has a detrimental effect on patients’ healthcare. The procedures that lead to drug allergy de-labelling are crucial for healthcare improvement and a reduction of inappropriate drug use. Up to now, drug allergy de-labelling via direct oral challenge has been widely performed for penicillins in children due to their massive use in childhood[6]. However, it is now well established that direct oral challenge is also safe in adults for penicillins[7]. Allergy de-labelling for other drugs than penicillins has been little studied. Safe cephalosporin allergy de-labelling has recently emerged[8]. However, large-scale drug allergy de-labelling is necessary due to the risk of inadequate use of drugs, particularly in critical situations. For the first time, we show that direct oral challenge to drugs other than penicillins is safe with the opportunity for patients to have access to effective drugs such as pain-killers or NSAIDs.\u003c/p\u003e\n\u003cp\u003eOur study also introduces the concept of large-scale drug allergy de-labelling in outpatient visits. Given the high number of patients with drug allergy labels, it is imperative to find the best way to de-label patients. The situation of the healthcare system in Europe and also the rest of the world is deteriorating due to the increased number of patients and the shortage of healthcare professionals, particularly in hospitals[9]. A direct drug challenge in an outpatient visit ensures a larger number of patients with drug allergy de-labelling and a reduction in healthcare professionals involved in care. For these reasons, our study provides data that will change the way in which drug allergy labelling is addressed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study has several limitations. We did not use a validated score such as PEN-FAST because there is no validated score for drugs other than penicillins[7]. Moreover, no placebo arms were used for our study.\u003c/p\u003e\n\u003cp\u003eIn conclusion, allergy de-labelling to all drugs in patients with low-risk allergies can be safely conducted in outpatient visits.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eDisclosure of interest:\u003c/h2\u003e \u003cp\u003eProf Guilleminault reports grants, personal fees and/or non-financial support from Astrazeneca, GSK, Novartis, Chiesi, Sanofi, Stallergenes, ALK, Bayer and MSD outside from the submitted work.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eNS: Conceptualisation; Investigation; Methodology; Project administration; Validation; Visualisation; Writing \u0026ndash; original draft; Writing \u0026ndash; review \u0026amp; editing; Data curation ResourcesMCV and MC: Investigation; Methodology; Project administration; Validation; Visualisation; Writing \u0026ndash; review \u0026amp; editingLG: Conceptualisation; Formal analysis; Investigation; Methodology; Project administration; Supervision; Validation; Visualisation; Writing \u0026ndash; original draft; Writing \u0026ndash; review \u0026amp; editing; Data curation Resources\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data will be available on request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDo\u0026ntilde;a I, Torres MJ, Celik G, Phillips E, Tanno LK, Castells M. Changing patterns in the epidemiology of drug allergy. Allergy. 2024;79(3):613\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKottapalli A, Warren CM, Nimmagadda SR, Bartell TR, Gupta RS. The distribution and determinants of physician-diagnosed drug allergy in a large, nationally representative sample of US children and adults. J Allergy Clin Immunol Pract. 2024;12(2):515\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStone CA Jr., Trubiano J, Coleman DT, Rukasin CRF, Phillips EJ. The challenge of de-labeling penicillin allergy. Allergy. 2020;75(2):273\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMacy 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(3): 790\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastells M, Khan DA, Phillips EJ. Penicillin Allergy. N Engl J Med. 2019;381(24):2338\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eProvidencia R, Aali G, Zhu F, Leas BF, Orrell R, Ahmad M, Bray JJH, Pelone F, Nass P, Marijon E, Cassandra M, Celermajer DS, Shokraneh F. Penicillin Allergy Testing and Delabeling for Patients Who Are Prescribed Penicillin: A Systematic Review for a World Health Organization Guideline. Clin Rev Allergy Immunol. 2024;66(2):223\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCopaescu AM, Vogrin S, James F, Chua KYL, Rose MT, De Luca J, Waldron J, Awad A, Godsell J, Mitri E, Lambros B, Douglas A, Youcef Khoudja R, Isabwe GAC, Genest G, Fein M, Radojicic C, Collier A, Lugar P, Stone C, Ben-Shoshan M, Turner NA, Holmes NE, Phillips EJ, Trubiano JA. Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial. JAMA Intern Med. 2023;183(9):944\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoraczewski J, Lee R, Koo G, Krantz MS, Allocco C, Phillips EJ, Stone CA. Jr. Direct oral challenges safely reduce the burden of low-risk cephalosporin allergy labels. J Allergy Clin Immunol Pract. 2025;13(9):2522\u0026ndash;e25252521.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArmitage R. The case for introducing a minimum NHS service requirement for UK-trained doctors. J Med Ethics 2025.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Characteristics of the total population. *\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"518\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 283px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eData\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal population\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=304\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 283px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e46.3 \u0026plusmn; 17.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 283px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e222 (73.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 283px;\"\u003e\n \u003cp\u003eAtopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e55 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 283px;\"\u003e\n \u003cp\u003eMastocytosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e1 (0.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 283px;\"\u003e\n \u003cp\u003eTime since the initial reaction\u003c/p\u003e\n \u003cp\u003e\u0026lt;1 year\u003c/p\u003e\n \u003cp\u003e1\u0026ndash;5 years\u003c/p\u003e\n \u003cp\u003e5\u0026ndash;10 years\u003c/p\u003e\n \u003cp\u003e\u0026gt;10 years\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e49 (16.1%)\u003c/p\u003e\n \u003cp\u003e27 (8.8%)\u003c/p\u003e\n \u003cp\u003e15 (4.9%)\u003c/p\u003e\n \u003cp\u003e169 (55.6%)\u003c/p\u003e\n \u003cp\u003e44 (14.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 283px;\"\u003e\n \u003cp\u003eTime between drug intake and symptoms for the initial reaction\u003c/p\u003e\n \u003cp\u003eImmediate\u003c/p\u003e\n \u003cp\u003eNon-immediate\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27 (8.9%)\u003c/p\u003e\n \u003cp\u003e114 (37.5 %)\u003c/p\u003e\n \u003cp\u003e163 (53.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 283px;\"\u003e\n \u003cp\u003eCulprit drugs\u003c/p\u003e\n \u003cp\u003ePenicillin\u003c/p\u003e\n \u003cp\u003eNSAIDs\u003c/p\u003e\n \u003cp\u003eOther antibiotics\u003c/p\u003e\n \u003cp\u003eCephalosporins\u003c/p\u003e\n \u003cp\u003eOthers*\u003c/p\u003e\n \u003cp\u003eAnalgesics (excluding NSAIDs)\u003c/p\u003e\n \u003cp\u003eCorticosteroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e228 (75.0%)\u003c/p\u003e\n \u003cp\u003e31 (10.2%)\u003c/p\u003e\n \u003cp\u003e15 (4.9%)\u003c/p\u003e\n \u003cp\u003e10 (3.3%\u003c/p\u003e\n \u003cp\u003e9 (3.0%\u003c/p\u003e\n \u003cp\u003e7 (2.3%)\u003c/p\u003e\n \u003cp\u003e4 (1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e*others : Pylera\u0026reg;, Fyremadel, Macrogol, Furosemide, Pantoprazole, Nitrofurantoine, Hydrochlorothiazide, Enoxaparine, Metoclopramide.\u003c/p\u003e\n\u003cp\u003eTable 2: details of patients with positive oral drug challenge\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"980\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDate of onset\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026gt; 10 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026gt; 10 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026gt; 10 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026lt; 1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e1-5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e1-5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026lt; 1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026gt; 10 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026gt; 10 years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInitial reaction delay\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003eImmediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003eImmediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eDelayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003eDelayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eDelayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eDelayed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003eDelayed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInitial reaction\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003eFacial erythema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003eSkin rash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eAngioedema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003eGeneralised erythema and facial angiodema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eGeneralised urticaria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003eTruncal urticaria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eVomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eUrticaria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSuspected drug\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003ePenicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003eAspirin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003ePenicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003eCotrimoxazole\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003ePylera (Bismuth, metronidazole, and tetracycline)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003eAmoxicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eKetoprofen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eAmoxicillin\u0026ndash;clavulanate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003ePenicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrug oral challenge\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003eAmoxicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003eAspirin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eAmoxicillin\u0026ndash;clavulanate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003eCotrimoxazole\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003ePylera (Bismuth, metronidazole, and tetracycline)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003eAmoxicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eKetoprofen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eAmoxicillin\u0026ndash;clavulanate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003eAmoxicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOnset of reaction following oral drug challenge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e30 minutes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e50 minutes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e30 minutes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e6 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e24 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e48 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e6 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e24 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e24 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDetails of the reaction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003eFacial erythema and nausea\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003eUrticarial papules on the abdomen and back\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eUrticaria on the trunk, back, and legs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003ePruritus and erythema of the trunk, face, and back\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eUrticaria of the lower limbs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003eGeneralized urticaria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eNausea, abdominal pain, and two episodes of vomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eMaculopapular rash and fever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003eGeneralized urticaria\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment administred\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003eH1-antihistamine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003eH1-antihistamine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eH1-antihistamine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003eH1-antihistamine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003eH1-antihistamine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n 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\u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"allergy-asthma-and-clinical-immunology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aaci","sideBox":"Learn more about [Allergy, Asthma \u0026 Clinical Immunology](http://aacijournal.biomedcentral.com/)","snPcode":"13223","submissionUrl":"https://submission.nature.com/new-submission/13223/3","title":"Allergy, Asthma \u0026 Clinical Immunology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"drug, allergy, challenge ","lastPublishedDoi":"10.21203/rs.3.rs-8852874/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8852874/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Although oral direct challenge has been adopted by numerous clinicians around the world in a context of drug hypersensitivity, drug allergy de-labelling remains largely confined to hospital-based care and mostly for penicillins\nIn this study, we aim to perform direct oral drug challenge (DODC) in patients with low-risk allergy to drugs (not only penicillin) in outpatient visits.\nWe conducted a prospective single-centre study from May 2022 to January 2024. Inclusion criteria were age ≥14 years and a label of drug allergy with an initial reaction compatible with an allergic reaction. Exclusion criteria were severe anaphylaxis or severe cutaneous adverse drug reactions or prior skin tests to the suspected drug. The culprit drug was given as a standard single dose in an outpatient hospital visit.\nIn total, 304 patients were included. Penicillins were the most frequent culprit drugs with 228 (75%) patients. The other drugs involved in allergy labelling were as follows: nonsteroidal anti-inflammatory drugs (NSAIDs) in 31 (10.2%) patients, cephalosporins in 10 (3.3%) patients, other antibiotics in 15 (4.9%) patients, analgesics in 7 (2.3%) patients and corticosteroids in 4 (1.3%) patients. Nine (3.0%) patients had a reaction with other drugs. Among the whole cohort, 295 (97.0%) had no reaction during DODC. Ten patients presented a mild reaction including three patients with an immediate reaction and six with a delayed reaction.\nIn conclusion, allergy de-labelling to all drugs in patients with low-risk allergies can be safely conducted in outpatient visits.","manuscriptTitle":"Drug allergy de-labelling with a direct oral challenge in outpatient hospital visits","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-26 18:29:26","doi":"10.21203/rs.3.rs-8852874/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-18T16:39:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-18T14:13:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-27T19:15:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"109441056127981899608996832685638735731","date":"2026-02-25T20:42:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329297589984796883589916252488061412414","date":"2026-02-23T22:13:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-23T18:09:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-18T14:18:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-18T14:17:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"Allergy, Asthma \u0026 Clinical Immunology","date":"2026-02-11T14:17:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"allergy-asthma-and-clinical-immunology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aaci","sideBox":"Learn more about [Allergy, Asthma \u0026 Clinical Immunology](http://aacijournal.biomedcentral.com/)","snPcode":"13223","submissionUrl":"https://submission.nature.com/new-submission/13223/3","title":"Allergy, Asthma \u0026 Clinical Immunology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8c70952e-3d52-4792-b238-27851e4cd39d","owner":[],"postedDate":"February 26th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-03-18T16:55:18+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-26 18:29:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8852874","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8852874","identity":"rs-8852874","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}