IFN-γ ELISpot-enabled machine learning for culprit drug identification in nonimmediate drug hypersensitivity.

BACKGROUND: Diagnosing drug-induced allergy, especially nonimmediate phenotypes, is challenging. Incorrect classifications have unwanted consequences. OBJECTIVE: We sought to evaluate the diagnostic utility of IFN-γ ELISpot and clinical parameters in predicting drug-induced nonimmediate hypersensitivity using machine learning. METHODS: The study recruited 393 patients. A positive patch test or drug provocation test (DPT) was used to define positive drug hypersensitivity. Various clinical factors were considered in developing random forest (RF) and logistic regression (LR) models. Performances were compared against the IFN-γ ELISpot-only model. RESULTS: Among the 102 patients who had 164 DPTs, most patients had severe cutaneous adverse reactions (35/102, 34.3%) and maculopapular exanthems (33/102, 32.4%). Common suspected drugs were antituberculosis drugs (46/164, 28.1%) and ß-lactams (42/164, 25.6%). Mean (SD) age of patients with DPT was 52.7 (20.8) years. IFN-γ ELISpot, fixed drug eruption, Naranjo categories, and nonsteroidal anti-inflammatory drugs were the most important features in all developed models. The RF and LR models had higher discriminating abilities. An IFN-γ ELISpot cutoff value of 16.0 spot-forming cells/106 PBMCs achieved 94.8% specificity and 57.1% sensitivity. Depending on clinical needs, optimal cutoff values for RF and LR models can be chosen to achieve either high specificity (0.41 for 96.1% specificity and 0.52 for 97.4% specificity, respectively) or high sensitivity (0.26 for 78.6% sensitivity and 0.37 for 71.4% sensitivity, respectively). CONCLUSIONS: IFN-γ ELISpot assay was valuable in identifying culprit drugs, whether used individually or incorporated in a prediction model. Performances of RF and LR models were comparable. Additional test datasets with DPT would be helpful to validate the model further.

Prevention of allergic reactions during oxaliplatin desensitization through inhibition of Bruton tyrosine kinase.

BACKGROUND: Acute infusion reactions to oxaliplatin, a chemotherapeutic used to treat gastrointestinal cancers, are observed in about 20% of patients. Rapid drug desensitization (RDD) protocols often allow the continuation of oxaliplatin in patients with no alternative options. Breakthrough symptoms, including anaphylaxis, can still occur during RDD. OBJECTIVE: Our aim was to evaluate whether pretreatment with acalabrutinib, a Bruton tyrosine kinase inhibitor, can prevent anaphylaxis during RDD in a patient sensitized to oxaliplatin. METHODS: A 52-year-old male with locally advanced gastric carcinoma developed anaphylaxis during his fifth cycle of oxaliplatin. As he required 6 additional cycles to complete his curative-intent treatment regimen, he underwent RDD to oxaliplatin but still developed severe acute reactions. The risks and benefits of adding acalabrutinib before and during RDD were reviewed, and the patient elected to proceed. RESULTS: With acalabrutinib taken before and during the RDD, the patient was able to tolerate oxaliplatin RDD without complication. Consistent with its mechanism of action, acalabrutinib completely blocked the patient's positive skin prick response to oxaliplatin. Acalabrutinib did not alter the percentage of circulating basophils (1.24% vs 0.98%) before the RDD but did protect against basopenia (0.74% vs 0.09%) after the RDD. Acalabrutinib was associated with a drastic reduction in the ability of basophils to upregulate CD63 in vitro following incubation with oxaliplatin (0.11% vs 2.38%) or polyclonal anti-human IgE antibody (0.08% vs 44.2%). CONCLUSIONS: Five doses of acalabrutinib, 100 mg, orally twice daily starting during the evening 2 days before and continuing through RDD allowed a sensitized patient to receive oxaliplatin successfully and safely.

Nonsteroidal anti-inflammatory drug "allergy" labeling is associated with increased postpartum opioid utilization.

BACKGROUND: Current guidelines recommend a stepwise approach to postpartum pain management, beginning with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), with opioids added only if needed. Report of a prior NSAID-induced adverse drug reaction (ADR) may preclude use of first-line analgesics, despite evidence that many patients with this allergy label may safely tolerate NSAIDs. OBJECTIVE: We assessed the association between reported NSAID ADRs and postpartum opioid utilization. METHODS: We performed a retrospective cohort study of birthing people who delivered within an integrated health system (January 1, 2017, to December 31, 2020). Study outcomes were postpartum inpatient opioid administrations and opioid prescriptions at discharge. Statistical analysis was performed on a propensity score-matched sample, which was generated with the goal of matching to the covariate distributions from individuals with NSAID ADRs. RESULTS: Of 38,927 eligible participants, there were 883 (2.3%) with an NSAID ADR. Among individuals with reported NSAID ADRs, 49.5% received inpatient opioids in the postpartum period, compared to 34.5% of those with no NSAID ADRs (difference = 15.0%, 95% confidence interval 11.4-18.6%). For patients who received postpartum inpatient opioids, those with NSAID ADRs received a higher total cumulative dose between delivery and hospital discharge (median 30.0 vs 22.5 morphine milligram equivalents [MME] for vaginal deliveries; median 104.4 vs 75.0 MME for cesarean deliveries). The overall proportion of patients receiving an opioid prescription at the time of hospital discharge was higher for patients with NSAID ADRs compared to patients with no NSAID ADRs (39.3% vs 27.2%; difference = 12.1%, 95% confidence interval 8.6-15.6%). CONCLUSION: Patients with reported NSAID ADRs had higher postpartum inpatient opioid utilization and more frequently received opioid prescriptions at hospital discharge compared to those without NSAID ADRs, regardless of mode of delivery.

Trends in Childhood Anaphylaxis in Singapore: 2015-2022.

BACKGROUND: There has been limited data regarding the incidence of anaphylaxis in Asia. We aim to describe patterns in patient characteristics, triggers and clinical presentation of childhood anaphylaxis in Singapore. METHODS: This was a retrospective review of emergency electronic medical records of children with anaphylaxis. Patients with the allergy-related diagnoses of anaphylaxis, angioedema, allergy and urticaria based on ICD-9 codes were screened. Cases fulfilling the World Allergy Organization criteria for anaphylaxis were included. RESULTS: A total of 1188 cases of anaphylaxis were identified with a median age of 6.3 years. Extrapolating data from the study sites, from 2015 to 2022, the incidence rate of childhood anaphylaxis emergency visits in Singapore doubled from 18.9 to 38.8 per 100,000 person-years, with an incidence rate ratio (IRR) of 2.06 (95% confidence interval [CI] 1.70-2.49). In 2022, the incidence rate of food anaphylaxis was 30.1 per 100,000 person-years, IRR 2.39 (95% CI 1.90-3.01) and drug anaphylaxis was 4.6 per 100,000 person-years, IRR 1.89 (95% CI 1.11-3.25). The incidence rate in children aged 0-4 years quadrupled during the study period. Common triggers were egg (10.4%), peanut (9.3%), tree nut (8.8%), milk (8%), shellfish (7.8%) and non-steroidal anti-inflammatory drug (4.4%). The majority (88.6%) of patients were treated with intramuscular adrenaline. Total number of allergy-related visits did not increase over time between 2015 and 2019. Rates of severe anaphylaxis, namely anaphylactic shock and admission to high-dependency and intensive care, did not increase over time, with a mean incidence of 1.6, IRR 0.85 (95% CI 0.40-1.83) and 0.7, IRR 1.77 (95% CI 0.54-5.76) per 100,000 person-years, respectively. CONCLUSION: While the number of emergency visits due to childhood anaphylaxis has increased, the number of cases of allergy-related visits, anaphylactic shock and anaphylaxis requiring high-dependency and intensive care did not rise.

Penicillin Allergy in China: Consequences of Inappropriate Skin Testing Practices and Policies.

Penicillins are the most frequently prescribed class of medications worldwide and first-line antibiotic of choice for most bacterial infections. They are also commonly labelled as the culprit of drug 'allergy'; leading to obligatory use of second-line antibiotics, suboptimal antibiotic therapy and increased antimicrobial resistance. However, the majority of reported penicillin 'allergy' labels are found to be incorrect after allergy testing, emphasising the importance of proper drug allergy testing and evaluation. Penicillin skin testing (PST) remains an important component of drug allergy diagnosis; however, its practice and policies significantly differ across the world. Inappropriate and non-evidence-based PST practices can lead to consequences associated with allergy mislabelling. Even within different regions of China, with a population exceeding 1.4 billion, there are marked differences in the implementation, execution and interpretation of PST. This review aims to examine the differences in PST between Mainland China, Hong Kong and the rest of the world. We critically analyse the current practice of 'pre-emptive' PST in Mainland China, which has a significant false-positive rate leading to high levels of penicillin allergy mislabelling. Non-evidence-based practices further compound the high false-positive rates of indiscriminatory PST. We postulate that inappropriate PST policies and practices may exacerbate the mislabelling of penicillin allergy, leading to unnecessary overuse of inappropriate second-line antibiotics, increasing antimicrobial resistance and healthcare costs. We advocate for the importance of more collaborative research to improve the contemporary workflow of penicillin allergy diagnosis, reduce mislabelling and promote the dissemination of evidence-based methods for allergy diagnosis.

Mast cell versus basophil activation test in allergy: Current status.

In the past two decades, we witnessed the evolution of the basophil activation test (BAT) from mainly research applications to a potential complementary diagnostic tool to document IgE-dependent allergies. However, BAT presents some technical weaknesses. Around 10%-15% of tested patients are non-responders, BAT can be negative immediately post-reaction and the use of fresh basophils, ideally analysed within 4 h of collection, restricts the number of tests that can be performed per sample. The need for fresh basophils is especially limiting when conducting batch analyses and interlaboratory comparisons to harmonize BAT methodology. These limitations significantly hinder the wider application of BAT and urge the development of alternative testing, such as the mast cell activation test (MAT). The essential difference between BAT and MAT is the heterogeneity of the starting material used to perform the assays. Mast cells are tissue-resident, so cannot be easily accessed. Current alternative sources for functional studies are generating primary human mast cells, differentiated from donor progenitor cells, or using immortalized mast cell lines. Hence, the methodological approaches for MAT are not only vastly different from BAT, but also different among MAT protocols. This review summarizes the advantages and disadvantages of BAT and MAT assays, dedicating special attention to elucidating the key differences between the cellular sources used and provides an overview of studies hitherto performed comparing BAT and MAT in the diagnosis of IgE-mediated food and drug allergies.

Adrenaline Auto-Injectors for Preventing Fatal Anaphylaxis.

Anaphylaxis affects up to 5% of people during their lifetime. Although anaphylaxis usually resolves without long-term physical consequences, it can result in anxiety and quality of life impairment. Rarely and unpredictably, community anaphylaxis can cause rapid physiological decompensation and death. Adrenaline (epinephrine) is the cornerstone of anaphylaxis treatment, and provision of adrenaline autoinjectors (AAI) has become a standard of care for people at risk of anaphylaxis in the community. In this article, we explore the effectiveness of AAIs for preventing fatal outcomes in anaphylaxis, using information drawn from animal and human in vivo studies and epidemiology. We find that data support the effectiveness of intravenous adrenaline infusions for reversing physiological features of anaphylaxis, typically at doses from 0.05 to 0.5 µg/kg/min for 1-2 h, or ~ 10 µg/kg total dose. Intramuscular injection of doses approximating 10 µg/kg in humans can result in similar peak plasma adrenaline levels to intravenous infusions, at 100-500 pg/mL. However, these levels are typically short-lived following intramuscular adrenaline, and pharmacokinetic and pharmacodynamic outcomes can be unpredictable. Epidemiological data do not support an association between increasing AAI prescriptions and reduced fatal anaphylaxis, although carriage and activation rates remain low. Taken together, these data suggest that current AAIs have little impact on rates of fatal anaphylaxis, perhaps due to a lack of sustained and sufficient plasma adrenaline concentration. Effects of AAI prescription on quality of life may be variable. There is a need to consider alternatives, which can safely deliver a sustained adrenaline infusion via an appropriate route.

Severe vitamin D deficiency increases the risk of severe cutaneous adverse reactions.

Vitamin D deficiency has been reported to be associated with allergic diseases and dermatological disorders. We investigated the role of vitamin D in drug-induced non-immediate hypersensitivity reactions by measuring serum vitamin D levels in 60 patients diagnosed with non-immediate drug hypersensitivity reactions and in 60 patients who tolerated the same medication without any allergic reactions. The results showed that serum vitamin D levels were significantly lower in patients with severe cutaneous adverse reactions (SCARs) (13.56 ± 6.23 ng/mL) compared to patients with mild reactions (17.50 ± 7.49 ng/mL) and the drug-tolerant control group (17.42 ± 7.28 ng/mL), with p values of 0.031 and 0.015, respectively. The proportion of severe vitamin D deficiency (< 10 ng/mL) was much higher in SCAR patients compared to drug-tolerant subjects (36.7% vs. 11.7%, p value = 0.005). After adjusting for age, gender, region of residence, and concurrent illnesses, patients with severe vitamin D deficiency had significantly increased in-hospital mortality (odds ratio 16.04; 95% CI, 1.25-206.12, p value = 0.03). In conclusion, the risk of developing SCARs and in-hospital mortality was increased in patients with severe vitamin D deficiency. Further investigations should be conducted to elucidate the role of vitamin D in the development of SCARs.

Impact of a drug allergy education course for non-specialists: Findings from ADAPT-A randomized crossover trial.

BACKGROUND: The consequences of drug allergy remain a global health concern. Drug allergy is often a neglected topic and many non-specialists lack sufficient knowledge or confidence in evaluating or managing this common condition. Evidence-based interventions to better equip non-specialists to tackle drug allergy are needed. The aim of the study is to evaluate the effectiveness of an intensive educational course on drug allergy knowledge and practice of non-specialists. METHODS: A randomized crossover trial (NCT06399601) was conducted among practicing physicians and nurses participating in an intensive drug allergy course-Advances in Drug Allergy & Penicillin Testing (ADAPT). Participants' baseline knowledge and self-reported practices were assessed with standardized questionnaires (scored from 0 to 100, with "satisfactory" defined as ≥60/100). Participants were randomized into two cohorts and attended ADAPT at different time points. Serial responses before and after the course were compared within and between cohorts. RESULTS: Seventy participants (25 physicians, 45 nurses) randomized into two groups completed the course. Baseline drug allergy knowledge (58.0 ± 19.9) and self-reported practice (36.9 ± 24.3) were unsatisfactory among non-specialists, with significantly lower scores from nurses than physicians in both domains (knowledge: 49.0 ± 17.4 vs. 74.0 ± 12.7; practice: 32.1 ± 21.3 vs. 53.3 ± 23.1; all p < 0.001). Following completion of ADAPT, participants demonstrated significant improvements in knowledge (58.0 ± 19.9 vs. 77.7 ± 15.9, p < 0.001) and self-reported practice (36.9 ± 24.3 vs. 71.0 ± 20.2, p < 0.001). All participants (100%) and 99% of participants agreed that the course improved their clinical knowledge and practice, respectively. CONCLUSIONS: ADAPT, an intensive drug allergy educational course was effective in improving drug allergy knowledge and practice for non-specialists. Further longitudinal studies are required to evaluate long-term impact.

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.

Exploring recent advances in drugs severe cutaneous adverse reactions immunopathology.

Severe cutaneous adverse reactions to drugs (SCARs) are rare but life-threatening delayed allergies. While they primarily affect the skin, they can also affect internal organs. Accordingly, they present with diverse clinical symptoms that vary not only between SCARs subtypes but also among patients. Despite the availability of topical and systemic treatments, these only address the symptoms and not the cause. To develop more effective therapies, it is necessary to elucidate the complexity of the pathophysiology of SCARs in relation to their severity. In line with the new type IV hypersensitivity reactions nomenclature proposed by the European Academy of Allergy and Clinical Immunology (EAACI), this review highlights the current insights into the intricate immune mechanisms engaged, the interplay between the culprit drug and genetic predisposition in drug presentation mechanisms, but also how external factors, such as viruses, are implicated in SCARs. Their relevance to the development of targeted medicine is also discussed.

Basophil Activation Test Is Inferior to Provocation Test in Diagnosing Aspirin Hypersensitivity.

INTRODUCTION: Diagnostic of aspirin (ASA) hypersensitivity is largely based on provocation tests. However, they have significant limitations including influence of medications, necessity of hospitalization, and safety issues. Basophil activation test (BAT) seems to be a promising in vitro alternative. It has already proven to be a useful tool for diagnosing IgE-mediated allergy to certain food and airborne allergens as well as insects venoms. The aim of the study was to assess performance of BAT in diagnosing aspirin hypersensitivity in comparison with current golden standard (oral provocation test, OPT). METHODS: The study group comprised 148 adult patients with suspicion of aspirin hypersensitivity, including 51 (36%) with chronic urticaria, 73 (51%) with asthma, and 55 (39%) with chronic sinusitis. The control group was 10 healthy adult patients who used NSAIDs during preceding year with good tolerance. BAT with ASA was conducted in all the participants. Additionally, in the study group, OPT was performed with cumulative dose of 1,000 mg of ASA. RESULTS: Out of 148 study group participants, 114 underwent BAT and ASA provocation with conclusive results acquired in both tests. In this group, the threshold for positive BAT was 4.9%. Sensitivity and specificity of BAT were found to be 55.9% and 75%, respectively, with a positive predictive value of 77% and a negative predictive value of 54%. The highest sensitivity (78%) was found in subgroup patients with chronic urticaria, while specificity was highest in the subgroup with chronic respiratory diseases (87%). CONCLUSION: Despite significant advantages of BAT such as safety, no influence of drugs, and objectivity, its performance makes it inferior to current standard in ASA hypersensitivity.

Negative Predictive Value of Single-Day Drug Provocation Test for Immediate and Non-Immediate Beta-Lactam Hypersensitivity Reactions in Children.

INTRODUCTION: Beta-lactam antibiotics (BLAs) commonly cause hypersensitivity reactions in children. These reactions are categorized into immediate reactions, which include urticaria, angioedema, bronchospasm, and anaphylaxis, and non-immediate reactions, such as maculopapular rashes and delayed-onset urticaria/angioedema. Rashes in children, often caused by infections, may be misdiagnosed as BLA allergy. However, over 90% tolerate the medication following an allergic evaluation. METHODS: We aimed to evaluate patients with negative single-day drug provocation test (sdDPT) results for subsequent reactions and to determine the negative predictive value (NPV) of sdDPT for immediate (less than 1 h) and non-immediate (more than 1 h) suspected BLA allergy. In addition, non-immediate reactions were assessed by classifying them as occurring within 1-6 h or after 6 h. Patients who underwent sdDPT for suspected BLA allergy and tested negative between 2019 and 2023 were included in the study. They were questioned via telephone interviews about their reuse of the tested drug. RESULTS: 404 patients who underwent sdDPT for suspected BLA allergy were evaluated. The NPV of BLA sdDPT was determined to be 97.3%. When patients were categorized based on the time interval between the last dose and the reaction, the NPV was 97% for those experiencing a reaction within the first hour of drug use and 96.7% for reactions occurring after more than 1 h. Non-immediate reactions were further evaluated, revealing an NPV of 98.7% for reactions occurring between 1 and 6 h, and 92.5% for reactions occurring after 6 h. CONCLUSION: Our findings demonstrate that sdDPT has a high NPV for both immediate and non-immediate reactions. However, the NPV of sdDPT was lower for reactions occurring more than 6 h after the last dose.

Clinical Relevance of Specific IgE in Penicillin Allergy Investigation.

INTRODUCTION: Patients with immediate type allergic reactions to penicillins are at risk of anaphylaxis on reexposure. Diagnostic gold standard is drug provocation test (DPT) if allergy is not diagnosed by other means, such as skin testing or in vitro testing with measurement of specific IgE. Specific IgE testing carries low risk for the patient and blood sampling can be performed in primary care, but it is reported to have low sensitivity. The aim of this study was to evaluate if clinical characteristics of patients with suspected allergic reactions to penicillin and elevated specific IgE to penicillins, differed from patients without specific IgE, to identify predictors for elevated specific IgE to penicillins. METHODS: Levels of specific IgE to five penicillins (penicillin G, penicillin V, amoxicillin, ampicillin, and penicillin minor determinants) were available for 9,100 patients. Using multiple logistic regression, clinical data from 430 patients in this group who had elevated specific IgE to one or more penicillins were compared to data from 4,094 patients without specific IgE to penicillins, who had undergone DPT with a penicillin. RESULTS: In total 5.2% of patients had elevated specific IgE to one or more penicillins. Significantly more patients with elevated specific IgE had a history of immediate type reactions (<2 h) (OR = 4.34, p < 0.001); circulatory symptoms (OR = 1.63, p = 0.03) or angioedema (OR = 1.46, p = 0.005). Also, significantly more patients with elevated specific IgE had been treated with adrenaline (OR = 2.21, p = 0.005), steroids (OR = 1.76, p < 0.001), or antihistamines (OR = 1.83, p < 0.001). CONCLUSION: A history of an immediate type reaction requiring treatment, combined with elevated specific IgE to one or more penicillins is suggestive of an IgE mediated penicillin allergy and further allergy investigations may not be needed. Specific IgE to penicillins may be used early in allergy investigation of patients with severe immediate type reactions to penicillins.

Diagnosis and Clinical Management of Drug Allergies in Obstetrics and Gynecology: An Expert Review.

Drug allergies, specifically antibiotic allergies, are frequently encountered in obstetrics and gynecology as10% of the United States population reports a penicillin allergy. This poses a particular challenge to the obstetrician-gynecologist as beta-lactam antibiotics are indicated as first-line therapy for the treatment and prevention of most specialty-specific infections. Alternative antibiotic use in the setting of a reported allergy, is not benign and has been associated with increased cesarean delivery, endometritis, wound complications, and increased lengths of hospital stay in pregnant patients, increased Group B Streptococcus sepsis, neonatal length of stay and neonatal lab draws in neonates born to allergic patients and increased surgical site infections in gynecologic patients. Furthermore, alternative antibiotic use leads to increased antibiotic resistance, toxicity and healthcare cost. . Administration of antibiotics in a patient with a history of a Type I immediate hypersensitivity reaction, however, poses the risk of anaphylaxis with repeat exposure. Fortunately, over 90% of patients who report a penicillin allergy are not truly allergic and would tolerate penicillins if administered. This can be due to either mislabeling of the index reaction as an allergy (when it was due to a drug intolerance or a viral exanthem) or due to waning Immunoglobulin E-mediated immunity over time. Given this, allergy evaluation is widely recommended, even in pregnancy. Allergy evaluation involves a detailed patient history and when appropriate allergy testing with skin testing and/or oral challenge. These tools when used appropriately have been found to be safe and effective in gravid as well as non-gravid individuals and result in increased use of first line antibiotics. Furthermore, even in the setting of a true penicillin allergy, cross-reactivity with cephalosporins is extremely low and estimated at 2-3% among patients with a verified penicillin allergy and significantly lower than this among patients with an unverified penicillin allergy. Guidelines support routine use of cephalosporins without testing or additional precautions in patients with an unverified nonanaphylactic penicillin allergy as well as routine use of structurally dissimilar cephalosporins (specifically ancef) even in patients with an anaphylactic penicillin allergy. In cases where there is no appropriate alternative antibiotic than to the one which the patient is allergic such as with syphilis in a penicillin allergic pregnant patient, desensitization can be performed. This process involves temporary induction of drug tolerance through exposure of small amounts of the allergen until a therapeutic dose is achieved and has been safely performed in pregnancy. Desensitization requires expert supervision and is most often performed in the intensive care setting with a multidisciplinary team. The other two most common antibiotic allergies encountered in obstetrics and gynecology are to cephalosporins and metronidazole. Cephalosporin allergies are managed similarly to penicillin allergies with readily available skin testing and oral challenge. Skin testing for metronidazole allergy lacks sensitivity and specificity and thus oral challenge or desensitization procedure is the preferred approach for low risk and high-risk patients respectively. When it comes to drug allergies, and specifically antibiotic allergies, the role of the obstetrician-gynecologist is to identify patients with a reported allergy and to refer patients to a specialist for further evaluation as soon as possible. Allergy evaluation by means of a detailed patient history and allergy testing (skin testing and/or oral challenge) when indicated has been shown to be safe and effective and is an important part of antibiotic stewardship.

The importance of clinical history in the diagnosis of drug hypersensitivity in children.

BACKGROUND: In case of suspected hypersensitivity reactions (HRs) to drugs, a challenging area for pediatricians is detecting relevant elements in the parent-reported history, in order to reach a definite diagnosis. We analyzed the concordance between the description of the HR and the medical reports documented at the time of the event. Furthermore, we studied any correlation between clinical history variables and the prediction of true allergy. METHODS: We retrospectively collected 50 charts of children referred to our Allergy Unit, after a previous access to the Emergency Department. We compared the description of the HR at acute phase to the history told by parents. Type and timing of the HR and culprit drug were classified as "known" or "unknown." The diagnosis was confirmed or excluded at the end of the investigations. Logistic regression analysis was performed to find any significant association. RESULTS: The type of the HR was known in 74%, the timing in 28%, and the culprit drug in 98%. We showed that having had a severe HR had an increased odds of remembering the timing; being older >6 years and having had an immediate HR had an increased odds of remembering the type; time to diagnostic was lower in patients whose parents remembered the type of HR. CONCLUSION: Our paper underlines the importance of an accurate anamnesis at the time of the event. Providing the physicians with a standardized Case Report Form could be a useful tool to simplify the diagnostic work-up and minimize mistakes due to lack of memory.

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.

Incidence of and risk factors for paediatric perioperative anaphylaxis in the USA.

BACKGROUND: Perioperative anaphylaxis is a serious and often life-threatening immediate hypersensitivity reaction. There are few published data on paediatric perioperative anaphylaxis (pPOA). We evaluated the incidence of and risk factors involved in the occurrence of pPOA within a large US national database. METHODS: Deidentified data from the US Nationwide Inpatient Sample from 2005 to 2014 were used to identify pPOA cases and to conduct a retrospective multivariate analysis of preselected independent variables. RESULTS: Among 3,601,180 surgeries and procedures in children aged 0-18 yr, 297 pPOA cases were identified for an incidence of one in 12,125 surgeries and procedures. Compared with controls, pPOA cases had an increased median length of stay (6 vs 2 days; P<0.001) and median hospital cost ($54 719 vs $5109; P<0.0001). The age groups between 6 and 12 yr (odds ratio [OR] 7.1; 95% confidence interval [CI] 3.9-12.9; P<0.001) and 13 and 17 yr (OR 8.5; 95% CI 4.7-15.2; P<0.001) were associated with increased odds of pPOA. Transplant (OR 46.3; 95% CI 20.8-102.9; P<0.001), cardiac (OR 16.4; 95% CI 7.5-35.9; P<0.001), and vascular (OR 15.2; 95% CI 7.5-30.7; P<0.001) procedures posed the highest risk for pPOA. Chronic pulmonary disease, coagulopathy, and fluid and electrolyte disorders were also associated with pPOA (OR 2.2; 95% CI 1.5-3.3; P<0.001). CONCLUSIONS: The incidence of pPOA was one in 12,125 cases. Risk factors included age, procedure type, and comorbidities.

A successful desensitization in an adult patient with ARA-C infusion reaction.

INTRODUCTION: Cytarabine (ARA-C) is an antimetabolite agent used especially in the treatment of hematologic malignancies. Infusion reactions have an important place among the side effects that may occur due to treatment. Clinical findings of infusion reactions resemble allergic reactions. CASE REPORT: 47-year-old male patient with a diagnosis of B-cell Acute Lymphoblastic Leukaemia developed infusion reaction during ARA-C treatment. MANAGEMENT & OUTCOME: There was no alternative treatment option for his existing malignant disease, we decided ARA-C desensitization. DISCUSSION: We would like to describe a successful desensitization protocol in an adult patient who experienced a reaction during ARA-C infusion.

Hypersensitivity reaction to Abiraterone, successful desensitization protocol in prostate cancer patient.

INTRODUCTION: In prostate cancer, androgens are key in the growth of both normal prostate and cancer cells. Abiraterone acetate inhibits CYP17, an important target in prostate cancer given its central role in the production of adrenal and tumor-derived androgens. Although abiraterone is generally well tolerated, common adverse effects such as hypertension, hypokalemia, and hepatotoxicity have been reported. CLINICAL CASE: We present the case of an 83-year-old Mexican man with high-volume EC IV prostate cancer resistant to castration, orchiectomy, and bone, liver, and lung metastases. First-line treatment with the CHAARTED scheme was indicated, by patient decision refuse chemotherapy treatment. On the fourth day of starting treatment, he developed pruritic erythematous macular skin lesions and urticaria on the posterior chest that resolved spontaneously. A generalized erythematous and pruritic maculopapular rash appeared 12 days after starting abiraterone, for which she was referred to allergies. MANAGEMENT AND RESULTS: An oral provocation test was performed for two days, presenting localized macular lesions eight hours after the administration of abiraterone. An oral desensitization protocol was carried out for ten days in which no hypersensitivity reactions were observed, thus achieving the successful administration of abiraterone.