Aspirin hypersensitivity: a practical guide for cardiologists.

Aspirin has been known for a long time and currently stays as a cornerstone of antithrombotic therapy in cardiovascular disease. In patients with either acute or chronic coronary syndromes undergoing percutaneous coronary intervention aspirin is mandatory in a dual antiplatelet therapy regimen for prevention of stent thrombosis and/or new ischaemic events. Aspirin is also currently a first-option antithrombotic therapy after an aortic prosthetic valve replacement and is occasionally required in addition to oral anticoagulants after implantation of a mechanical valve. Presumed or demonstrated aspirin hypersensitivity is a main clinical problem, limiting the use of a life-saving medication. In the general population, aspirin hypersensitivity has a prevalence of 0.6%-2.5% and has a plethora of clinical presentations, ranging from aspirin-exacerbated respiratory disease to anaphylaxis. Although infrequent, when encountered in clinical practice aspirin hypersensitivity poses for cardiologists a clinical dilemma, which should never be trivialized, avoiding-as much as possible-omission of the drug. We here review the epidemiology of aspirin hypersensitivity, provide an outline of pathophysiological mechanisms and clinical presentations, and review management options, starting from a characterization of true aspirin allergy-in contrast to intolerance-to suggestion of desensitization protocols.

Differences in hypersensitivity reactions and gadolinium deposition disease/symptoms associated with gadolinium exposure to gadolinium-based contrast agents: new insights based on global databases VigiBase, FAERS, and IQVIA-MIDAS.

BACKGROUND: Hypersensitivity reactions (HSRs) can occur unexpectedly and be life-threatening when gadolinium-based contrast agents (GBCAs) are used. Gadolinium deposition disease (GDD) and symptoms associated with gadolinium exposure (SAGE) have been controversial for a long time. However, similar studies are currently incomplete or outdated. Therefore, comparing the safety of different GBCAs in terms of HSRs and GDD/SAGE using the latest post-marketing safety data should yield further insights into safely using GBCAs. METHODS: The safety differences between all GBCAs to GDD and the spectrum of GBCA-related HSRs were all compared and analyzed by using the World Health Organization database VigiBase and the FDA Adverse Event Reporting System (FAERS) database in this study. A further analysis of SAGE was also conducted using FAERS data. The lower limit of the reporting odds ratio (ROR) 95% confidence interval was used for signal detection. Moreover, the frequency of HSRs was calculated by dividing the number of reports in VigiBase by the total sales volume (measured in millions) from 2008 to 2022 in the IQVIA Multinational Integrated Data Analysis System. All adverse events were standardized using the Medical Dictionary for Drug Regulatory Activities (MedDRA) 26.0. RESULTS: This study shows that all GBCAs have the potential to induce HSRs, with nonionic linear GBCAs exhibiting a comparatively lower signal. According to standardized MedDRA query stratification analysis, gadobutrol had a greater ROR025 for angioedema. The ROR025 of gadobenate dimeglumine and gadoteridol is larger for anaphylactic/anaphylactoid shock conditions. Regarding severe cutaneous adverse reactions, only gadoversetamide and gadodiamide showed signals in FAERS and VigiBase. There were also differences in the frequency of HSRs between regions. Regarding GDD, gadoterate meglumine, and gadoteridol had a lower ROR025. An analysis of the 29 preferred terms linked to SAGE indicated that special consideration should be given to the risk of skin induration associated with gadoversetamide, gadopentetate dimeglumine, gadobenate dimeglumine, gadodiamide, and gadoteridol. Additionally, gadodiamide and gadoteridol pose a greater risk of skin tightness compared to other GBCAs. CONCLUSIONS: The risk differences among GBCAs using data from several sources were compared in this study. However, as a hypothesis-generating method, a clear causal relationship would require further research and validation.

Identifying the most at-risk age-group and longitudinal trends of drug allergy labeling amongst 7.3 million individuals in Hong Kong.

BACKGROUND: Incorrect drug 'allergy' labels remain a global public health concern. Identifying regional trends of drug allergy labeling can guide appropriate public health interventions, but longitudinal or population drug allergy studies remain scarce. We analysed the serial epidemiology of drug allergy labeling to identify specific subgroups at highest risk of drug allergy labeling for potential interventions. METHODS: Longitudinal, population-wide drug allergy labels and clinical data from over 7,337,778 individuals in Hong Kong between 2016 and 2021 were analysed. RESULTS: The absolute prevalence and incidence of documented drug allergy were 5.61% and 277/100,000 population, respectively. Annual incidence of new allergy labels was stable between 2016 and 2019, until a significant drop in 2020 (-16.3%) during the COVID19 pandemic. The most common allergy labels were anti-infectives (245,832 [44.5%]), non-steroidal anti-inflammatory (106,843 [19.3%]), and nervous system drugs (45,802 [8.3%]). The most common labeled culprits for the most severe immediate-type (anaphylaxis) and non-immediate-type (Stevens-Johnson syndrome) reactions were beta-lactams and nervous system drugs, respectively. For individuals at highest risk of labeling, there was significantly higher incidence of overall drug and beta-lactam allergy labeling amongst individuals aged > 40 years which contributed to the majority of newly labeled allergies (377,004, 68.2%). CONCLUSIONS: Contrary to traditional dogma, we identified disproportionately higher incidence of drug allergy labeling amongst older individuals, rather than the paediatric age group. We advocate for more population-wide drug allergy studies to investigate this phenomenon in other cohorts as well as future preventative and delabeling efforts focusing on the adult population.

Changing patterns in the epidemiology of drug allergy.

Drug allergy (DA) remains a complex and unaddressed problem worldwide that often deprives patients of optimal medication choices and places them at risk for life-threatening reactions. Underdiagnosis and overdiagnosis are common and due to the lack of standardized definitions and biomarkers. The true burden of DA is unknown, and recent efforts in data gathering through electronic medical records are starting to provide emerging patterns around the world. Ten percent of the general population engaged in health care claim to have a DA, and the most common label is penicillin allergy. Up to 20% of emergency room visits for anaphylaxis are due to DA and 15%-20% of hospitalized patients report DA. It is estimated that DA will increase based on the availability and use of new and targeted antibiotics, vaccines, chemotherapies, biologicals, and small molecules, which are aimed at improving patient's options and quality of life. Global and regional variations in the prevalence of diseases such as human immunodeficiency virus and mycobacterial diseases, and the drugs used to treat these infections have an impact on DA. The aim of this review is to provide an update on the global impact of DA by presenting emerging data on drug epidemiology in adult and pediatric populations.

Prior drug allergies are associated with worse outcome in patients with idiosyncratic drug-induced liver injury: A machine learning approach for risk stratification.

The impact of prior drug allergies (PDA) on the clinical features and outcomes of patients who develop idiosyncratic drug-induced liver injury (DILI) is largely unknown. We aimed to assess the clinical presentation and outcomes of DILI patients based on the presence or absence of PDA and explore the association between culprit drugs responsible for DILI and allergy. We analysed a well-vetted cohort of DILI cases enrolled from the Spanish DILI Registry. Bootstrap-enhanced least absolute shrinkage operator procedure was used in variable selection, and a multivariable logistic model was fitted to predict poor outcomes in DILI. Of 912 cases with a first episode of DILI, 61 (6.7%) had documented PDA. Patients with PDA were older (p = 0.009), had higher aspartate aminotransferase (AST) levels (p = 0.047), lower platelet count (p = 0.011) and higher liver-related mortality than those without a history of drug allergies (11% vs. 1.6%, p < 0.001). Penicillin was the most common drug associated with PDA in DILI patients (32%). A model including PDA, nR-based type of liver injury, female sex, AST, total bilirubin, and platelet count showed an excellent performance in predicting poor outcome in patients from the Spanish DILI Registry (area under the ROC curve [AUC] 0.887; 95% confidence interval [CI] 0.794 - 0.981) and the LATINDILI Network (AUC 0.932; 95% CI 0.884 - 0.981). Patients with suspected DILI should be screened for PDA as they would require a close monitoring for early detection of worsening clinical course.

Direct oral challenge for immediate and non-immediate beta-lactam allergy in children: A real-world multicenter study.

BACKGROUND: Allergy to beta-lactam antibiotics (BLA) is frequently suspected in children, but a drug provocation test (DPT) rules it out in over 90% of cases. Direct oral DPT (DODPT), without skin or other previous tests, is increasingly been used to delabel non-immediate BLA reactions. This real-world study aimed to assess the safety and effectiveness of DODPT in children with immediate and non-immediate reactions to BLAs. METHODS: Ambispective registry study in children (<15 years), attended between 2016 and 2023 for suspected BLA allergy in 15 hospitals in Spain that routinely perform DODPT. RESULTS: The study included 2133 patients with generally mild reactions (anaphylaxis 0.7%). Drug provocation test with the implicated BLA was performed in 2014 patients (94.4%): 1854 underwent DODPT (86.9%, including 172 patients with immediate reactions). One hundred forty-five (7.2%) had symptoms associated with DPT, although only four reactions were severe: two episodes of anaphylaxis and two of drug-induced enterocolitis syndrome, which resolved rapidly with treatment. Of the 141 patients with mild reactions in the first DPT, a second DPT was considered in 87 and performed in 57, with 52 tolerating it without symptoms. Finally, BLA allergy was ruled out in 90.9% of the sample, confirmed in 3.4%, and remained unverified, usually due to loss to follow-up, in 5.8%. CONCLUSIONS: Direct oral DPT is a safe, effective procedure even in immediate mild reactions to BLA. Many reactions observed in DPT are doubtful and require confirmation. Severe reactions are exceptional and amenable to treatment. Direct oral DPT can be considered for BLA allergy delabeling in pediatric primary care.

Local anesthetics allergy in children: Evaluation of diagnostic tests with Real-Life data.

BACKGROUND: Local anesthetic (LA) drugs are commonly used in clinical practice to provide effective analgesia, including in dentistry and minor surgical procedures. The perception of a high risk of allergy in daily applications leads to the referral of atopic patients and those with other drug allergies to allergy clinics for the evaluation of allergic reactions to LA. The aim of this study was to determine who should be referred to the allergy clinic for LA allergy testing, assess the frequency of LA allergy in pediatric patients, and identify the negative predictive value of skin tests in diagnosis. METHODS: January 2017-July 2023, the clinical and laboratory data, as well as the results of drug allergy tests, of patients referred to our pediatric allergy clinic by dentists and physicians performing minor surgical procedures with suspected LA allergy were retrospectively evaluated. RESULTS: Our study included a total of 153 patients, comprising 84 girls (54.9%) and 69 boys (45.1%), with a mean age of 8.9 (±3.3) years. The most common reason for referral was a history of non-LA drug allergies (n = 66, 43.2%), followed by asthma (n = 25, 16.3%). Hypersensitivity reactions (HRs) with LA were most commonly associated with articaine (n = 7, 4.8%), followed by lidocaine (n = 6, 4.1%). When intradermal tests were evaluated, 17 patients (11.1%) had a positive test result. The positivity for lidocaine was 70.6% (n = 12), and prilocaine was 29.4% (n = 5). Subcutaneous provocation was administered to 109 patients (71.2%), and one patient exhibited local erythema and swelling with prilocaine. CONCLUSION: Although LA allergy is a rare occurrence, consultations of this nature are frequently requested from allergy clinics in real life. Considering the negative predictive value of skin tests performed with LA drugs, the reaction rate appears to be low in patients with atopy or other drug allergies. It is crucial for all relevant healthcare professionals to be knowledgeable about the appropriate approach to suspected LA allergies to avoid unnecessary tests. To the best of our knowledge, our study is the most comprehensive work in the literature that evaluates the results of diagnostic tests in children referred with a suspicion of LA allergy.

Antibiotic allergy prevalence and documentation quality in Massachusetts long-term care facilities: A cross-sectional survey.

BACKGROUND: Antimicrobial resistance poses a significant global health challenge, particularly affecting older adults who are more susceptible to infections and their complications. Accurate diagnosis and documentation of antibiotic allergies are essential for effective antimicrobial stewardship. Despite the recognized overdiagnosis of antibiotic allergies, comprehensive studies on this subject in long-term care (LTC) settings are limited. OBJECTIVE: To determine the point prevalence of antibiotic allergies and documentation quality in Massachusetts LTC facilities. METHODS: We conducted a cross-sectional, 1-day point prevalence survey from July 1, 2023, to March 31, 2024, across 20 participating LTC facilities in Massachusetts in partnership with the Massachusetts Department of Public Health. The survey assessed the prevalence and documentation of antibiotic allergies among 2345 residents. Multivariable logistic regression was used to explore associations between documented penicillin allergy and demographic factors, including non-penicillin antibiotic allergies. RESULTS: The overall point prevalence of documented antibiotic allergies was 39.1%, with the most frequently reported classes being penicillins at 23.1%, sulfonamides at 15.4%, and cephalosporins at 5.2%. Significant documentation gaps were identified, with up to 92.8% of the allergy records found to be incomplete. Factors associated with documented penicillin allergies included female sex (adjusted odds ratio [aOR], 1.50; 95% CI, 1.16-1.94), White race (aOR, 1.92; 95% CI, 1.25-2.94), having allergies to non-penicillin antibiotics (aOR, 2.89; 95% CI, 2.33-3.59), and receipt of antibiotic (aOR, 2.13; 95% CI, 1.68-2.71). CONCLUSION: The high prevalence of documented antibiotic allergies and the notable deficiencies in their documentation underscore the urgent need for enhanced antibiotic evaluation, documentation practices, and penicillin delabeling in LTC facilities.

Epidemiology of perioperative anaphylaxis in France in 2017-2018: the 11th GERAP survey.

BACKGROUND: Perioperative anaphylaxis is rare but is associated with significant morbidity. This complication has been well described in France by the GERAP (Groupe d'Etude des Réactions Anaphylactiques Périopératoires), a network focused on its study. The epidemiology of perioperative anaphylaxis is evolving, influenced by environmental factors and clinical practice. The aim of this study was to update the epidemiology of perioperative anaphylaxis in France. METHODS: This multicentre retrospective study was performed in 26 allergy clinics of the GERAP network in 2017-8. RESULTS: There were 765 patients with perioperative anaphylaxis included. Most cases were severe, with 428 (56%) reactions graded as 3 or 4 according to the Ring and Messmer classification. Skin test results were available for 676 patients, with a culprit agent identified in 471 cases (70%). Neuromuscular blocking agents were the main cause of perioperative anaphylaxis (n=281; 60%), followed by antibiotics (n=118; 25%) and patent blue dye (n=11; 2%). Cefazolin was the main antibiotic responsible for perioperative anaphylaxis (52% of antibiotic-related reactions). Suxamethonium and rocuronium were the main neuromuscular blocking agents responsible for perioperative anaphylaxis with 7.1 (6.1-8.4) and 5.6 (4.2-7.4) reactions per 100,000 vials sold, respectively, whereas cefazolin-related cases were estimated at 0.7 (0.5-0.9) reactions per 100,000 vials sold. CONCLUSIONS: Our results confirm that most commonly identified triggering agents remain neuromuscular blocking agents. Reactions to antibiotics, particularly cefazolin, are becoming increasingly frequent. The origin of sensitisation to cefazolin is unknown, as no cross-sensitisation has been described, and it should be the subject of further study. Perioperative anaphylaxis should be followed over the years and understood given the changing triggers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04654923).

Relationship between fasting prior to contrast-enhanced CT and adverse reaction in patients with allergies history.

AIM: To examine the relationship between fasting prior to contrast-enhanced CT (CECT) and adverse reaction (AR) in patients with allergies history. MATERIALS AND METHODS: Patients with allergies history who underwent CECT from January 2014 to December 2020 (713 cases with iodinated contrast media (ICM)-related allergy history and 27045 cases with unrelated allergies history) were retrospectively analyzed. The occurrence of ICM-related AR and patient information were recorded. The relationship between fasting and AR and emetic complications was analyzed. RESULTS: There was no statistical difference in the overall incidence of AR and emetic complications between fasting group and non-fasting group (P>0.05) and fasting was not an influence factor for overall AR occurrence in patients with both ICM-related and unrelated allergies history. However, the incidence of severe AR in fasting group was higher than that in non-fasting group (P=0.01) in patients with unrelated allergies history. The AR incidence in fasting group was higher than that in non-fasting group (P=0.022) when receiving abdominal examinations in patients with unrelated allergies history. There was no statistical difference in the incidence of AR with different occurrence time between fasting group and non-fasting group (P>0.05) in patients with both ICM-related and unrelated allergies history. CONCLUSIONS: Fasting was associated with higher incidence of severe AR and was associated with higher AR incidence when receiving abdominal examinations in patients with unrelated allergies history. Fasting did not have effects on the occurrence time of AR in patients with allergies history. These provided new guidance for usage of ICM in patients with allergies history.

Additional use of extrinsic warmer for intravenous CT contrast media and its impact on incidence of contrast extravasations and allergic like reactions: a prospective observational case control study.

AIMS: To prospectively determine whether extrinsic warming of the low-osmolality CT contrast media (Iohexol 350, Iodixanol 320, Iopromide 300, and Iopamidol 300) to 37°C prior to intravenous administration affects extravasation and allergic-like reaction rates. MATERIALS AND METHODS: This large scale prospective case control study of adverse events included all the patients between the age group of 15-80 years undergoing routine contrast-enhanced computed tomographic (CECT) examinations from April 2018 to March 2020 at our institute. Ex vivo experiments were also performed to demonstrate change in contrast viscosity and fluid dynamics in relation to temperature. RESULTS: A total of 24,379 CECTs were conducted during the study period. Extrinsic warming showed a significant decrease in extravasation rates for Iohexol 350 at flow rates <3.5 mL/sec (P=0.037). No significant difference was observed with Iopromide 300 (P=0.432). Overall, a significant decrease in allergic reactions and overall contrast-related reactions (excluding physiologic reactions) was noted (P<0.001), with Iohexol 350. However, no significant difference was found with Iopromide 300. The most common physiological reaction was a sense of warmth, more prevalent in the warmed group, aligning with ex-vivo experiments demonstrating decreased viscosity with contrast warming. CONCLUSIONS: Extrinsic warming of contrast helps reduce the incidence of allergic-like reactions and extravasations for Iohexol 350, but no significant difference was noted with Iopromide 300 even at low injection rates (<3.5 mL/sec).

Polymorphisms of HLA genes and hypersensitivity to penicillin among patients in a Taiwanese population.

Penicillin allergy is a potentially life-threatening condition that is common among patients. However, the genetic associations with penicillin allergy are not yet recognized for prevention or diagnosis, particularly in East Asian populations. We conducted a retrospective case-control study using data from the Taiwan Precision Medicine Initiative and analysing DNA samples to identify eight major MHC Class I and Class II loci. We employed imputation methods for accurate HLA typing and enrolled 17,827 individuals who received penicillin. Logistic regression analyses were utilized to explore associations between HLA genotypes, comorbidities and allergy risk, while simultaneously conducting a subgroup analysis to explore the association between HLA genotypes, comorbidities and the severity of allergic reactions. Our study assigned 496 cases to the penicillin allergy group and 4960 controls to a matched group. The risk of penicillin allergy was significantly higher with HLA-DPB1*05:01 (OR = 1.36, p = .004) and HLA-DQB1*05:01 (OR = 1.54, p = .03), with adjusted p-values of .032 and .24, respectively. Urticaria was identified as a separate risk factor (OR = 1.73, p < .001). However, neither the HLA alleles nor the comorbidities had a significant relationship with the risk of severe penicillin-induced allergy. HLA-DPB1*05:01 was found to be significantly associated with penicillin allergy reactions among the Taiwanese population.

Perioperative hypersensitivity in children: A prospective multidisciplinary study.

BACKGROUND: There are few studies of perioperative hypersensitivity reactions in children. The diagnosis of perioperative hypersensitivity reactions may be under estimated because it is difficult to recognize the reactions. Anaphylaxis may go unnoticed because of patient unconsciousness. Urticaria may be missed due to sterile drapes. The aim of this study was to prospectively evaluate perioperative hypersensitivity reactions. METHODS: In this prospective study, patients with suspected perioperative hypersensitivity reactions aged 0-18 years who underwent surgery at the Department of Pediatric Surgery, Cerrahpasa Faculty of Medicine, between 2019 and 2021 were investigated. Suspected reactions in the perioperative period were graded according to the Ring and Messmer scale. Patients with suspected reactions were examined 4-6 weeks after the reaction. If necessary, specific IgE and basophil activation tests were performed. Reactions of grades III-IV were considered anaphylaxis. If one test modality was strongly positive and there was a relevant time point or repeated allergic reactions, or at least two test modalities were positive, hypersensitivity was confirmed. In all patients, serum tryptase levels were analyzed at the time of the reaction, 2 h after the reaction, and 4-6 weeks after the reaction as part of the allergic evaluation. RESULTS: A total of 29 patients (8 female, 21 male) suspected of having an intraoperative reaction during the study were included in the analysis. Perioperative hypersensitivity reactions were noted in 1 patient. The incidence of perioperative hypersensitivity reactions was reported to be 0.03% (n = 1/2861). While anaphylaxis was confirmed in 1 patient, 5 patients were considered possible anaphylaxis cases. CONCLUSION: Perioperative hypersensitivity reactions can be life-threatening and may recur with further administration. Collaboration between pediatric surgeons, anesthesiologists, and allergists can prevent further reactions. All suspected cases should be evaluated by an experienced allergist soon after the initial reaction.

Adult penicillin allergy programmes in Australian hospitals: a practical guide from the National Antibiotic Allergy Network.

Penicillin allergy is a significant burden on patient, prescribing and hospital outcomes. There has been increasing interest in the incorporation of penicillin allergy testing (i.e. delabelling) into antimicrobial stewardship (AMS) programmes to reduce the burden of penicillin allergy labels and improve prescribing. In particular, there has been a focus on point-of-care penicillin allergy assessment and direct oral challenge for low-risk phenotypes. The National Antibiotic Allergy Network has provided a guide to assist AMS clinicians with the incorporation of penicillin allergy programmes, in particular direct oral challenge, into Australian hospitals.

Comparison of allergy prevalence using brinzolamide 1.0% / brimonidine 0.2% fixed combination with and without ß-blocker in glaucoma patients: a retrospective cohort study.

BACKGROUND: Glaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent ß-blocker. METHODS: Of these, 176 patients used a ß-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent ß-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan-Meier survival analysis. RESULTS: Allergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent ß-blocker-usage groups, respectively. Kaplan-Meier survival analysis indicated that half of the allergies in the concurrent ß-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent ß-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent ß-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent ß-blocker-usage group. CONCLUSIONS: Concurrent use of ß-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of ß-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education.

Impact of institutional interventions on the rate of paclitaxel hypersensitivity reactions.

PURPOSE: Paclitaxel is associated with hypersensitivity reactions (HSRs). Intravenous premedication regimens have been devised to decrease the incidence and severity of HSRs. At our institution oral histamine 1 receptor antagonists (H1RA) and histamine 2 receptor antagonists (H2RA) were adopted as standard. Standardizations were implemented for consistent premedication use in all disease states. The purpose of this retrospective study was to compare the incidence and severity of HSRs before and after standardization. METHODS: Patients who received paclitaxel from 20 April 2018 to 8 December 2020 having an HSR were included in analysis. An infusion was flagged for review if a rescue medication was administered after the start of the paclitaxel infusion. The incidences of all HSR prior to and post-standardization were compared. A subgroup analysis of patients receiving paclitaxel for the first and second time was performed. RESULTS: There were 3499infusions in the pre-standardization group and 1159infusions in the post-standardization group. After review, 100 HSRs pre-standardization and 38 HSRs post-standardization were confirmed reactions. The rate of overall HSRs was 2.9% in the pre-standardization group and 3.3% in the post-standardization group (p = 0.48). HSRs, during the first and second doses of paclitaxel, occurred in 10.2% of the pre-standardization and 8.5% of the post-standardization group (p = 0.55). CONCLUSIONS: This retrospective interventional study demonstrated that same-day intravenous dexamethasone, oral H1RA, and oral H2RA are safe premedication regimens for paclitaxel. No change in the severity of reactions was seen. Overall, better adherence to premedication administration was seen post-standardization.

Epidemiology and Triggers of Severe Perioperative Anaphylaxis: An 8-Year Single-Center Study.

OBJECTIVE: To determine the features, rescue measures, outcomes, re-allergic reactions, and independent risk factors associated with severe anaphylaxis during surgery. DESIGN: Instances of severe perioperative anaphylaxis were identified through perioperative electronic records, adverse event reporting records, and surveys of anesthesiologists. Confirmed cases were randomly matched 4:1 with control cases on the same operation day. Patient risk factors, surgery type, anesthetic technique, and perioperative medications, fluids, and blood transfusions were given in instances of severe perioperative anaphylaxis were compared with control cases. SETTING: A tertiary hospital in China. PATIENTS: All patients undergoing surgery and anesthesia in the operating room from January 2014 to February 2022. MEASUREMENTS: Incidence and the independent risk factors for severe perioperative anaphylaxis. MAIN RESULTS: Ninety-seven patients experienced severe perioperative allergic responses during the 266,033 surgeries performed, with an incidence rate of 3.6 per 10,000. Three of 97 anaphylaxis patients experienced a severe allergic reaction again during the second surgery. The nested case-control study revealed that the independent triggers during surgery were allergy history (odds ratio 5.23; 95% confidence interval [CI], 2.35-11.68; p < 0.001), cisatracurium use (odds ratio 5.03; 95% CI, 1.22-20.70; p < 0.001), hydroxyethyl starch 130/0.4 use (odds ratio 5.36; 95% CI, 2.99-9.60; p =0.025), and allogeneic plasma (odds ratio 11.02; 95% CI, 3.78-35.95; p < 0.001). CONCLUSIONS: Perioperative severe anaphylaxis is a rare but life-threatening complication. Previous allergic history, cisatracurium, hydroxyethyl starch 130/0.4, and allogeneic plasma may be the independent triggers. Early diagnosis of anaphylaxis and the timely administration of epinephrine are critical to allergic treatment. Avoiding exposure to allergens is effective for preventing severe allergic responses and the efficacy of glucocorticoids and antihistamines is controversial.

Evaluation of different protocols for classification of pediatric hypersensitivity reactions to nonsteroidal anti-inflammatory drugs: Children with underlying allergic disease should be a separate subgroup.

Background: Different recommendations for the classification of nonsteroidal anti-inflammatory drug hypersensitivity reactions (NSHSR) in children have been reported but a shortage still exists. Objective: The aim of the present study was to evaluate the inclusivity of two European Academy of Allergy and Clinical Immunology (EAACI) position paper classifications and to characterize the factors that underlie classification discordance in children. Methods: Patients with a history of NSHSR were evaluated with a standardized diagnostic protocol according to EAACI/ European Network for Drug Allergy (ENDA) recommendations. Children were classified and compared according to the EAACI 2013 and the pediatric EAACI/ENDA 2018 classifications. Subjects who were unclassified and those who were classified were compared. Results: Of 232 patients (median [interquartile range] age 6 years (4-11 years) with a history of NSHSR, 52 (22.4%) were confirmed with diagnostic tests. Thirty-six (69.2%) were classified as having cross-intolerance, whereas 16 patients (30.8%) were classified as selective responders. Eleven of the confirmed cases (21.2%) could not be categorized according to the 2013 EAACI classification, whereas this number was six adolescents (11.5%) when the 2018 EAACI/ENDA pediatric classification was used. Patients who were unclassified and who were all cross-intolerant were more likely to have atopic sensitization (p = 0.001) and asthma as an underlying disease (p = 0.03), higher serum eosinophil count (p = 0.022), and total immunoglobulin E levels (p = 0.007) compared with those who fit well into the classification. In multivariate regression analysis, the presence of atopic sensitization (adjusted odds ratio 20.36 [95% confidence interval, 2.14-193.48]; p = 0.009) was found to be the only significant underlying factor for an unclassified and/or blended phenotype. Conclusion: The 2013 EAACI classification resulted in a high rate of subjects who were unclassified. Despite better clinical utility, the recent pediatric EAACI/ENDA classification system still has shortcomings in terms of inclusivity for adolescents. Mostly, children with underlying allergic diseases could not be classified by the current guidelines. We propose to classify them as a separate pediatric cross-intolerance subgroup because the underlying mechanism may involve more than cyclooxygenase 1 inhibition.

Inpatient allergy delabeling of pediatric patients with low-risk penicillin allergy status through direct oral amoxicillin challenge.

Background: Less than 5% of children who report penicillin allergy have clinically pertinent type 1 immunoglobulin E mediated hypersensitivity reaction by using direct oral amoxicillin challenge. Several pathways have been developed to delabel penicillin allergy by using direct oral amoxicillin challenge, mostly in the outpatient settings, but there is relative scarcity on published outcomes of these pathways, especially in the inpatient pediatric settings. Objective: This study aimed to evaluate the performance of an institutionally derived inpatient penicillin allergy screening tool. Methods: Patients were stratified into three penicillin allergy risk categories by using an institutional screening questionnaire. Patients with a no-risk status were delabeled without challenge testing. Patients with low-risk status underwent direct graded oral amoxicillin challenge and delabeled based on their response. Patients with high-risk status were referred to allergy service. Results: Ninety-two patients were identified with penicillin allergy. Forty of the 92 patients (43%) were screened. Of the 40 patients screened, 6 (15%) were identified as no risk, 28 (70%) were identified as low risk, and 6 (15%) were identified as high risk. Twenty-four of the 28 patients at low risk (86%) were eligible for direct amoxicillin oral challenge. Seventeen of the 24 (71%) consented to oral challenge but only 12 (71%) underwent direct amoxicillin oral challenge. Eleven of the 12 who underwent oral challenge (92%) were successfully delabeled. Five of the six patients at no risk (83%) were successfully delabeled. Three of the six patients at high risk (50%) were referred for further allergy evaluation. Overall, 16 of the 40 patients screened (40%) were successfully delabeled. Conclusion: In this small pediatric inpatient study, our institutional risk stratification screening tool identified patients at low risk for penicillin allergy and direct graded oral amoxicillin challenge was safely administered to delabel penicillin allergy in these patients.Clinical trial NCT05020327, www.clinicaltrials.gov.

Characteristics of childhood anaphylaxis in different age groups.

BACKGROUND: Anaphylaxis is a severe systemic hypersensitivity reaction that usually has a rapid onset and can be fatal. Presentations of childhood anaphylaxis vary widely in accordance with the triggers and the patient's age, geographical region and dietary and lifestyle habits. METHODS: The medical records of 177 paediatric patients diagnosed with anaphylaxis between January 2021 and January 2024, whose disease progression was monitored at a single tertiary care centre, were reviewed retrospectively. RESULTS: The study included 177 patients diagnosed with anaphylaxis (107 males and 70 females with a median age of 48 months). The most common allergen responsible was food (53.7%). Egg allergy was the most common source of anaphylaxis, afflicting 35 patients (19.3%), while beta-lactam provoked the most common drug allergy, affecting 24 patients (13.6%). The most common organ involved was the skin (92.7%). When the patients were analysed by age group, there were more males in the infancy, preschool and school age groups, while there were more females in the adolescent group (p = 0.44). Food-induced anaphylaxis became less common with increasing age, whereas the rate of drug-induced anaphylaxis increased (p = 0.01 and p = 0.01, respectively). Cardiovascular system findings were observed more frequently in adolescents compared to other age groups (p = 0.003). Most cases stemming from a food allergy were mild, whereas most drug-induced cases were moderate or severe (p < 0.05). When severity was analysed by age group, mild cases in infants were more common than moderate to severe cases. CONCLUSION: The aetiological and clinical manifestations of childhood anaphylaxis vary among different age groups.