Beta-lactam Antibiotic Allergy Research Articles

Effects of Sex and Gender in Immediate Beta-Lactam Antibiotic Allergy: A Systematic Review and Meta-analysis

BackgroundBeta-lactams are the most common antibiotic class reported to cause allergic drug reactions. Previous literature suggests an increased prevalence of penicillin drug allergy in female patients in both inpatient and outpatient settings. However, the effects of sex and gender have not been well characterized regarding the entire class of beta-lactam antibiotics. ObjectiveThis systematic review and meta-analysis aimed to identify sex and gender-based differences in the prevalence of immediate beta-lactam allergy. MethodsWe performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library between 2013-2023. Patients with a documented beta-lactam allergy who underwent allergy testing with skin testing, oral drug challenge, or serum-specific IgE were included. We quantitatively assessed sex- and gender-based differences in beta-lactam allergy with meta-analysis. ResultsWe included 69 primary studies, assessing 53,989 participants from outpatient and inpatient cohorts. 7,558 patients had a confirmed beta-lactam allergy. There was no difference in the prevalence of positive beta-lactam allergy test between males and females. Sub-group analysis of studies that performed oral challenges did show a higher risk of beta-lactam allergy in females than males (RR 1.40, 95% CI 1.18-1.66, p < 0.001, I2 =77.8%). Finally, there was a higher proportion of females (64.8%) than males enrolled in beta-lactam allergy studies. ConclusionsOur findings suggest both sex-based and gender-based differences in the prevalence of immediate beta-lactam allergy. Both biological factors, such as sex hormones, and gender-based behaviors, including increased healthcare utilization, may contribute to higher rates of beta-lactam allergy diagnosis in females.

Drug Allergies in Older Adults: A Major Problem in a Specific Population

Introduction: The use of medications in older adults is increasing due to the prevalence of chronic diseases. Data on the characteristics of drug allergies (DAs) in older adults are limited. This study investigated the prevalence and clinical characteristics of DAs in patients aged 65 years and older. Methods: Patient records were examined retrospectively between January 2018 and December 2022. The study included 200 patients aged ≥18 years who met the criteria for diagnosis of type B drug reactions. The patients were divided into two groups: the adult group (18–64 years) and the older adult group (≥65 years). Results: Advanced age was an independent risk factor for the development of anaphylaxis and immediate and delayed hypersensitivity reactions (odds ratio [OR] = 4.296; 95% confidence interval [CI] = 1.700–10.855; p = 0.002, OR = 3.800; 95% CI = 1.247–11.579; p = 0.019, OR = 3.028; 95% CI = 1.248–7.343; p = 0.014, respectively). Older adults had higher rates of comorbidities and polypharmacy (p < 0.001, p = 0.016, respectively), beta-lactam antibiotic allergy (p < 0.001), and hospitalization and intensive care unit (ICU) admission for DAs (p = 0.024, p = 0.045, respectively). Conclusion: Older age was an independent risk factor for anaphylaxis and both immediate and delayed reactions. Older adults had higher rates of comorbidities, polypharmacy, beta-lactam antibiotic triggers, and hospitalization and ICU admission.

Comparing Skin and Serum Testing to Direct Challenge Outcomes in Children With β-Lactam Allergies

BackgroundThere is a scarcity of prospective studies investigating the relative roles of skin prick and intradermal testing, serum-specific Immunoglobulin E, and extended oral challenges in diagnosing children with reported beta-lactam allergies. ObjectiveTo determine the sensitivity and specificity of skin testing and serum-specific Immunoglobulin E in children with beta-lactam allergies, with immediate and non-immediate historic reactions. MethodsFour hundred children with parent-reported beta-lactam allergies were recruited into an open-label prospective study. Detailed allergy histories were collected. Those with medically observed and documented histories of anaphylaxis, requiring epinephrine, or SCARs were excluded. In total, 380 children underwent all testing modalities and a direct provocation test. Each child was followed up for a minimum of three years. ResultsTrue allergy in children was uncommon, 8·3% reacted to the direct provocation challenge or the 5-day extended oral provocation challenge. Children reporting cephalosporin allergy or a reaction within one year were more likely to react to direct provocation testing. The sensitivity, specificity, and positive predictive value of skin testing was 12·5%, 98·8% and 20·0% for direct challenge outcomes, 4·76%, 99·0% and 25·0% for extended challenge outcomes, and 6·9%, 99·0% and 40·0% for both challenges combined. Follow-up investigations revealed that 5·7% of children had a mild repeat reaction and 2·7% continued to avoid the culprit despite successful delabeling. The relabeling rate for children readmitted to hospital was 15% with the relabeing being unfounded. ConclusionGenuine beta-lactam allergies were rare, with over 90% of children effectively delabeled. Skin and serum-specific Immunoglobulin E testing did not aid the diagnosis of beta-lactam antibiotic allergy in children, regardless of medical history. Extended oral challenges proved valuable in confirming allergies and boosted parental confidence.

Beta-lactam allergy risk stratification in a maternity population in Australia: Scope for allergy de-labelling.

Unconfirmed beta-lactam allergy in pregnant people has been associated with higher morbidity, unnecessary exposure to broad-spectrum antibiotics and prolonged hospitalisation. There are no published data on beta-lactam allergies in pregnant people in Australia. The aim was to describe patient-reported beta-lactam allergies and appropriateness for antibiotic allergy de-labelling in a maternity cohort in Australia. Maternity patients aged ≥18 years admitted to our institution between March 2021 and June 2021 with a beta-lactam allergy documented in their electronic medical record were interviewed for details of their allergy. The documented allergies were compared to the allergy history obtained from the interview. Severity of the allergy was rated, and appropriateness for allergy de-labelling was assessed using the Victorian Therapeutics Advisory Group beta-lactam antibiotic allergy assessment tool. One hundred and fifty-three beta-lactam allergies (182 reactions) were reported by 145 patients. Penicillin class antibiotics were the most frequently implicated, including unspecified penicillins (95/153, 62%), amoxicillin (19/153, 13%) and amoxicillin-clavulanate (8/153, 5%). Allergy documentation required amending in 52 of 145 patients (36%); 85 of 153 (56%) of the beta-lactam allergies were considered low risk and potentially appropriate for direct oral re-challenge. Beta-lactam allergies were inaccurately documented in more than one third of the maternity patients included in our study. As such, education of maternity care providers about the importance of accurate allergy history taking remains an urgent unmet need. Furthermore, allergy assessment and de-labelling during pregnancy should be considered in maternity patients to optimise antibiotic prescribing and to improve maternal and neonatal health outcomes.

1237. Inpatients with a beta-lactam antibiotic allergy label (BAAL) and unrevealed tolerance: A prevalence study aimed to prioritize non-invasive delabeling for antimicrobial stewardship programs

Abstract Background This study aimed to use data analytics to retrospectively identify the prevalence of inpatients across a system of hospitals with a BAAL who received and tolerated the culprit or related beta-lactam (BL) without proper documentation in the allergy profile of the electronic medical record (EMR). Findings from this study could prioritize direct non-invasive delabeling opportunities as a feasible process measure for resource limited antimicrobial and diagnostic stewardship programs (ADSP). Methods Eligible patients were generated by a data analyst using the Northwestern Medicine (NM) Enterprise Data Warehouse. Patients eligible for inclusion: 1) adults &amp;gt; 18 years of age, 2) inpatients at a NM System Hospital (NMSH) with &amp;gt; 1 overnight stay between 8/1/2020 and 8/1/2022, 3) a BAAL in the allergy profile of the EMR, and 4) received &amp;gt; 1 dose of a BL during the study period. Patients who only received aztreonam were excluded. The primary objective of this study was to determine the prevalence of inpatients with a BAAL who received and tolerated the culprit BL antibiotic during the study period without proper documentation in the allergy profile of the EMR. The secondary objectives were 1) to determine the prevalence of inpatients with a BAAL who received and tolerated a related BL antibiotic during the study period without proper documentation in the allergy profile of the EMR and 2) to determine the prevalence of reported BL allergy reactions and severity risk. Results Results of our study identified up to 751 inpatient BAALs (9.7%), including 87 BAALs of high priority, as valuable targets for early direct non-invasive delabeling, requiring minimal effort and resources from ADSP. Conclusion Using data analytics to empirically assess digital allergy information could streamline the antimicrobial stewardship process, proactively identifying and prioritizing BAALs to cast a wider net and efficiently achieve process measure outcomes related to allergies compared to conventional methods of delabeling. Disclosures Anju T. Peters, MD MSCI, Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Optinose: Advisor/Consultant|Sanofi Regeneron: Advisor/Consultant|Sanofi Regeneron: Grant/Research Support

1221. Non-severe, non-immune mediated intolerances: simple targets for direct non-invasive delabeling opportunities of beta-lactam antibiotic allergy labels (BAAL)

Abstract Background Majority of patients with a BAALs can tolerate a β-lactam without concerns for a severe IgE-mediated reaction. Many BAALs are confirmed to be intolerances or adverse events versus a true allergy. False BAALs can result in the use of alternative non-BLs, posing risk for collateral health consequences. Current strategies to delabel a false BAAL can be restricted, time consuming and invasive, requiring skin and drug provocation testing. An alternative approach involves direct delabeling of reported BL allergies in patients with non-severe, non-immune mediated intolerances. This method of assessment relies on the review of the electronic medical record (EMR) versus invasive assessments. The aim of this study was to identify the prevalence of reported non-severe, non-immune mediated intolerances across a system of hospitals for prospective non-invasive delabeling opportunities. Methods Eligible patients seen within the Northwestern Medicine Healthcare System (NMHS) between 8/1/20 and 8/1/22 were included. Eligible patients: 18 years and older, admitted to a NMHS hospital with &amp;gt; 1 overnight stay, and a BAAL in the allergy profile of the EMR. Examples of non-severe, non-immune mediated intolerances were GI upset, rash w/o pruritus, headache, and pharmacologically predictable reactions. Demographic and allergy data reported in the allergy profile of the EMR was retrospectively obtained through from the Epic Enterprise Data Warehouse. Results Over the study period, 25,768 unique patients were eligible for inclusion. During this time, the NMHS admitted 194,670 patients, suggesting a BAAL prevalence rate of 13.2% system-wide. Included patients were mostly White (81%), female (65%) with a median age of 64 (18-109). Of the 25,768 BAALs, 16,561 (64%) were reported as immune mediated reactions, 2,534 (9.8%) as non-severe, non-immune mediated intolerances, 3,405 (13.2%) as indeterminant, and 3,268 (12.7%) had no reaction type reported in the allergy profile of the EMR. Conclusion Our prevalence of BAAL across NMHS hospitals was 13.2%. At least 2,534 BAALs reported as a non-severe, non-immune mediated intolerance could be directly delabeled using a non-invasive approach, possibly offering a simpler and broader approach compared to current (invasive) strategies. Disclosures All Authors: No reported disclosures

Interval Assessment of Beta-Lactam Antibiotic Allergy Status and De-labeling Process of Pediatric Patients in Children's Hospital of Pittsburgh between 2020 – 2022.

Beta-lactam allergy is associated with suboptimal medical care and increased healthcare expenses. We hypothesize that introducing a multidisciplinary institutional beta-lactam de-labeling protocol at Children's Hospital of Pittsburgh (CHP) would lead to increased percentage of de-labeling encounters.

Direct oral challenges for assessing amoxicillin allergy in adults

The most appropriate strategy for the diagnosis of beta lactam allergy remains unclear. A study was conducted on a cohort evaluating the use of graded oral challenge (GOC) to diagnose beta-lactam antibiotic allergy among adults presenting with an isolated benign skin rash (defined as symptoms limited to the skin consisting of a non-vesicular eruption).

Assessment of the validity of the beta-lactam antibiotic allergy assessment tool for use in the rural context, QLD.

The objective of the study was to validate a clinical aid to guide the assessment and management of a patient's listed beta-lactam antibiotic allergy for use in rural areas of Australia. Rural generalists, pharmacists and junior doctors completed an online assessment of eight patient case studies using the tool. The study was conducted in the Southern Downs, QLD. Twenty-seven rural generalists, nine pharmacists and eight junior doctors. The sensitivity of the selected allergy phenotype and management option for each case study was calculated by profession and overall. Hazardous responses were reported by management category and profession. The sensitivity overall for phenotype selection was 82.4% (95% CI, 78.0-86.2) and for management 88.1% (95% CI, 84.2-91.2). The sensitivity for phenotype selection was lower for junior doctors than other professions 73.4% (95% CI, 60.9-83.7), but did not reach statistical significance (p=0.08). A total of 10/308 responses for management recommended the least restrictive option of direct delabelling or oral challenge, where the correct answer was skin prick testing or referral to an allergist. With further education the tool could be a key component of increased antimicrobial stewardship in rural areas in Australia.

The Long-term Impact of Beta-lactam Antibiotic Allergy Testing - A Matched Case-control Study

The Long-term Impact of Beta-lactam Antibiotic Allergy Testing - A Matched Case-control Study

Matched Case-Control Study of the Long-Term Impact of Beta-Lactam Antibiotic Allergy Testing.

Whereas the short-term impacts of antibiotic allergy testing on delabeling and antibiotic usage have been demonstrated, the long-term impacts have been less well defined. In a single-center matched case-control study from Melbourne, Australia, we demonstrate that a beta-lactam antibiotic allergy testing program has a significant impact on antibiotic usage and infection-related outcomes. This study supports implementation of an antibiotic allergy testing program as a standard of care of antimicrobial stewardship programs.

Prevalence and Impact of Reported Drug Allergies among Rheumatology Patients.

Background: Drug allergies (DA) are immunologically mediated adverse drug reactions and their manifestations depend on a variety of drug- and patient-specific factors. The dysregulated immune system underpinning rheumatological diseases may also lead to an increase in hypersensitivity reactions, including DA. The higher prevalence of reported DA, especially anti-microbials, also restricts the medication repertoire for these already immunocompromised patients. However, few studies have examined the prevalence and impact of reported DA in this group of patients. Methods: Patients with a diagnosis of rheumatoid arthritis (RA), spondyloarthritis (SpA), or systemic lupus erythematosus (SLE) were recruited from the rheumatology clinics in a tertiary referral hospital between 2018 and 2019. Prevalence and clinical outcomes of reported DA among different rheumatological diseases were calculated and compared to a cohort of hospitalized non-rheumatology patients within the same period. Results: A total of 6081 patients (2541 rheumatology patients: 1286 RA, 759 SpA, and 496 SLE; and 3540 controls) were included. DA was more frequently reported among rheumatology patients compared to controls (23.8% vs. 13.8%, p < 0.01). Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) were the two most commonly reported categories of DA with a prevalence of 12.0% and 5.1%, respectively. Reported antibiotics allergies were more frequent in patients with RA (OR = 1.20, 95% CI = 1.02–1.62, p = 0.03) and SLE (OR = 4.69, 95% CI = 3.69–5.95, p < 0.01); and associated with increased infection-related admissions among rheumatology patients (OR = 1.79, 95% CI = 1.09–2.95, p = 0.02). Among the subgroup of patients referred for allergy testing, 85.7% of beta-lactam antibiotic allergy labels were found to be inaccurate and de-labelled after negative drug provocation testing. Conclusion: The prevalence of reported DA was significantly higher in rheumatology patients. Reported antibiotic allergy was associated with increased rate of infection-related admissions. However, the rate of genuine antibiotic allergy was low. Further studies are needed to guide proper assessment of reported DA and impact of comprehensive allergy testing in this group of patients.

Criteria for intradermal skin testing and oral challenge in patients labeled as fluoroquinolone allergic

Allergy to fluoroquinolones (FQs) is the most frequently reported non–beta-lactam antibiotic allergy.1 The basic FQ structure is a bicyclic skeleton and can be classified by generation, with later generations correlating with broader gram-positive and anaerobic antimicrobial spectrum in particular.1 Interpretation of hypersensitivity reactions to FQs is likely complicated by non–IgE-mediated reactions because all FQs are small-molecule ligands for the mast cell G-protein–coupled receptor MRGPRX2 and have been shown to lead to direct mast cell activation in both in vitro models with the human MRGPRX2 receptor and murine models.

Guideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Society of Allergology (AeDA), German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Austrian Society for Allergology and Immunology (ÖGAI), and the Paul-Ehrlich Society for Chemotherapy

This guideline on diagnostic procedures for suspected beta-lactam antibiotic (BLA) hypersensitivity was written by the German and Austrian professional associations for allergology, and the Paul-Ehrlich Society for Chemotherapy in a consensus procedure according to the criteria of the German Association of Scientific Medical Societies. BLA such as penicillins and cephalosporins represent the drug group that most frequently triggers drug allergies. However, the frequency of reports of suspected allergy in patient histories clearly exceeds the number of confirmed cases. The large number of suspected BLA allergies has a significant impact on, e.g., the quality of treatment received by the individual patient and the costs to society as a whole. Allergies to BLA are based on different immunological mechanisms and often manifest as maculopapular exanthema, as well as anaphylaxis; and there are also a number of less frequent special clinical manifestations of drug allergic reactions. All BLA have a beta-lactam ring. BLA are categorized into different classes: penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors with different chemical structures. Knowledge of possible cross-reactivity is of considerable clinical significance. Whereas allergy to the common beta-lactam ring occurs in only a small percentage of all BLA allergic patients, cross-reactivity due to side chain similarities, such as aminopenicillins and aminocephalosporins, and even methoxyimino cephalosporins, are more common. However, the overall picture is complex and its elucidation may require further research. Diagnostic procedures used in BLA allergy are usually made up of four components: patient history, laboratory diagnostics, skin testing (which is particularly important), and drug provocation testing. The diagnostic approach – even in cases where the need to administer a BLA is acute – is guided by patient history and risk – benefit ratio in the individual case. Here again, further studies are required to extend the present state of knowledge. Performing allergy testing for suspected BLA hypersensitivity is urgently recommended not only in the interests of providing the patient with good medical care, but also due to the immense impact of putative BLA allergies on society as a whole.

Guideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics

This guideline on diagnostic procedures for suspected beta-lactam antibiotic (BLA) hypersensitivity was written by the German and Austrian professional associations for allergology, and the Paul-Ehrlich Society for Chemotherapy in a consensus procedure according to the criteria of the German Association of Scientific Medical Societies. BLA such as penicillins and cephalosporins represent the drug group that most frequently triggers drug allergies. However, the frequency of reports of suspected allergy in patient histories clearly exceeds the number of confirmed cases. The large number of suspected BLA allergies has a significant impact on, e.g., the quality of treatment received by the individual patient and the costs to society as a whole. Allergies to BLA are based on different immunological mechanisms and often manifest as maculopapular exanthema, as well as anaphylaxis; and there are also a number of less frequent special clinical manifestations of drug allergic reactions. All BLA have a beta-lactam ring. BLA are categorized into different classes: penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors with different chemical structures. Knowledge of possible cross-reactivity is of considerable clinical significance. Whereas allergy to the common beta-lactam ring occurs in only a small percentage of all BLA allergic patients, cross-reactivity due to side chain similarities, such as aminopenicillins and aminocephalosporins, and even methoxyimino cephalosporins, are more common. However, the overall picture is complex and its elucidation may require further research. Diagnostic procedures used in BLA allergy are usually made up of four components: patient history, laboratory diagnostics, skin testing (which is particularly important), and drug provocation testing. The diagnostic approach—even in cases where the need to administer a BLA is acute—is guided by patient history and risk–benefit ratio in the individual case. Here again, further studies are required to extend the present state of knowledge. Performing allergy testing for suspected BLA hypersensitivity is urgently recommended not only in the interests of providing the patient with good medical care, but also due to the immense impact of putative BLA allergies on society as a whole.

Pathways to improved antibiotic allergy and antimicrobial stewardship practice: The validation of a beta-lactam antibiotic allergy assessment tool

The validation of a beta-lactam antibiotic allergy assessment allows non-allergists to effectively phenotype patient-reported antibiotic allergies and direct them to appropriate ‘de-labeling’ stratergies.

Serious Infections of Hospitalized Patients Are Associated with a Higher Prevalence of Reported Beta Lactam Antibiotic Allergy

Serious Infections of Hospitalized Patients Are Associated with a Higher Prevalence of Reported Beta Lactam Antibiotic Allergy

Penicillin and beta-lactam allergy: epidemiology and diagnosis.

Penicillin is the most common beta-lactam antibiotic allergy and the most common drug class allergy, reported in about 8% of individuals using health care in the USA. Only about 1% of individuals using health care in the USA have a cephalosporin allergy noted in their medical record, and other specific non-penicillin, non-cephalosporin beta-lactam allergies are even rarer. Most reported penicillin allergy is not associated with clinically significant IgE-mediated reactions after penicillin rechallenge. Un-verified penicillin allergy is a significant and growing public health problem. Clinically significant IgE-mediated penicillin allergy can be safely confirmed or refuted using skin testing with penicilloyl-poly-lysine and native penicillin G and, if skin test is negative, an oral amoxicillin challenge. Acute tolerance of an oral therapeutic dose of a penicillin class antibiotic is the current gold standard test for a lack of clinically significant IgE-mediated penicillin allergy. Cephalosporins and other non-penicillin beta-lactams are widely, safely, and appropriately used in individuals, even with confirmed penicillin allergy. There is little, if any, clinically significant immunologic cross-reactivity between penicillins and other beta-lactams. Routine cephalosporin skin testing should be restricted to research settings. It is rarely needed clinically to safely manage patients and has unclear predictive value at this time. The use of alternative cephalosporins, with different side chains, is acceptable in the setting of a specific cephalosporin allergy. Carbapenems and monobactams are also safely used in individuals with confirmed penicillin allergy. A certain predictable, but low, rate of adverse reactions will occur with all beta-lactam antibiotic use both pre- and post-beta-lactam allergy evaluations.

Desensitization in patients with beta-lactam drug allergy

BackgroundPatients with a history of beta-lactam antibiotic allergy are often admitted to the hospital with severe or life-threatening infections requiring beta-lactam antibiotics. Strict avoidance of beta lactams to such patients may prevent them from getting adequate coverage and can lead to an increase in the use of alternative antibiotics, which can predispose to antibiotic resistance. Past studies revealed a lower incidence of pen allergy then patients’ histories suggest. Fortunately today, there are three options for patients presenting with a history of beta-lactam allergy. Penicillin skin testing, beta-lactam challenge or beta-lactam desensitization.Recently Pre Pen has been FDA re-approved and when combined with Pen G is a valid way to determine if patients are able to tolerate beta-lactam antibiotic. When these agents are not available one must decide about desensitization or challenge. When a patient has a positive penicillin skin test, desensitization or beta-lactam avoidance are the only options.This paper reviews the safety of beta-lactam desensitization. ObjectiveTo perform a chart review on patients desensitised with beta lactam to determine if desensitizations can be performed safely without minimal complications. MethodsA retrospective chart review was performed on allergy and immunology inpatient consultations for beta-lactam desensitization between September 2003 and August 2006 at the Cedars-Sinai Medical Centre in Los Angeles. Patient data and outcomes of desensitization were analysed. ResultsA total of 13 intravenous desensitizations were performed on 12 patients. The patients consisted of eight females and four males with an average age of 65 years. Age range was 36–92 years old. All 13 intravenous desensitizations were completed without complications. No patient required a slower rate of desensitization or discontinuance of the desensitization. Patients were able to tolerate the initial therapeutic dose of their beta-lactam antibiotic and were then able to complete full therapeutic courses of their antibiotic. ConclusionBeta-lactam antibiotic sensitivity continues to present a challenging problem for physicians. Patients with drug resistant infections who are unable to obtain skin testing or who test positive to skin tests may need either a challenge or desensitization. Desensitization, saved for those with a convincing beta-lactam hypersensitivity history is often the choice of last resort given the associated cost and risk of anaphylaxis. However, once desensitization is complete, patients are usually able to tolerate full doses of antibiotics for full treatment length with minimal side effects.

Oral drug challenges in non‐steroidal anti‐inflammatory drug‐induced urticaria, angioedema and anaphylaxis

Urticaria, angioedema and anaphylaxis are common adverse reactions to non-steroidal anti-inflammatory drugs (NSAIDs). To investigate the clinical characteristics of NSAID-induced acute hypersensitivity reactions with structured oral drug challenges. Patients with NSAID-induced urticaria, angioedema or anaphylaxis were challenged with either the homologous NSAID to confirm diagnosis or a heterologous NSAID to investigate cross-reactivity. Data were analysed retrospectively and supplemented by a telephone questionnaire. Sixty-eight patients (mean age 48.3, 53 females) reported a total of 75 instances of NSAID-induced reactions of which 64% were purely cutaneous and 36% were systemic anaphylaxis. Ibuprofen was the most frequent cause of reactions (35%), however, diclofenac was the most frequent cause of anaphylaxis (48%). Seventeen out of 40 (43%) homologous NSAID challenges were positive; presentation with anaphylaxis or reaction to diclofenac predicted a positive challenge. Only 7 of 28 (25%) of heterologous NSAID challenges were positive. Structured challenges enabled us to identify 23 (34%) patients with selective reactivity to a single NSAID, 19 (28%) patients with cross-reactivity to multiple NSAIDs and 23 (34%) patients in whom NSAID hypersensitivity was not reproduced. Selective reactors presented most often with anaphylaxis and some had a background of beta-lactam antibiotic allergy. Cross-reactive patients often had a background of chronic urticaria and presented with milder reactions. In the absence of a reliable in vitro test, structured drug challenges allow identification of selective and cross-reactive NSAID hypersensitivity syndromes. NSAID-induced anaphylaxis is often associated with selective hypersensitivity and patients may not need to avoid other NSAIDs.