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Background: About 10% of patients have a penicillin allergy label, but less than 5% of them are actually allergic. Unnecessary penicillin avoidance is associated with serious medical consequences. Given the growing number of these labels, it is imperative that our diagnostic strategy for penicillin allergy be as efficient as possible. The validity of traditionally used skin tests (STs) has been questioned, whereas drug provocation testing (DPT), the criterion standard, without previous ST appears very safe in most cases., Objective: To evaluate the safety of direct DPT without consideration for ST results and the validity of ST in the diagnosis of penicillin allergy., Methods: In this prospective cohort study without a control group, we recruited patients consulting an allergist for penicillin allergy. Patients underwent ST followed by DPT regardless of ST results. Patients with anaphylaxis to penicillin within the past 5 years or a severe delayed reaction were excluded, as were those with significant cardiorespiratory comorbidity., Results: None of the 1002 recruited patients had a serious reaction to DPT. Ten (1.0%) had a mild immediate reaction, of whom only 1 (0.1%) was considered likely IgE-mediated. The positive and negative predictive values of ST for an immediate reaction were 3.6% and 99.1%, respectively., Conclusions: In a low-risk adult population reporting penicillin allergy, ST has very poor positive predictive value. Direct DPT without ST is safe and appears to be an ideal diagnostic strategy to remove penicillin allergy labels that could be implemented in first-line practice., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: There is currently no standardized duration of drug provocation test (DPT) for confirming/delabeling beta-lactam hypersensitivity reaction (BL-HSR)., Objectives: This meta-analysis and systematic review aimed to investigate the added diagnostic value of extended-day over single-day DPT for confirming/delabeling BL-HSR in adults and children., Methods: The MEDLINE, EMBASE, Web of Science, and CINAHL online databases were searched from inception to March 15, 2023, for studies that performed extended-day DPT to confirm/delabel BL-HSR. Risk difference and risk ratio were used to compare the proportions of patients with confirmed BL-HSR by single-day or extended-day DPT., Results: A total of 10,371 DPTs from 42 studies were included. Extended-day DPTs ranged from 2 to 7 days, or as long as index reactions were reported (maximum 10 days). The overall prevalence of confirmed BL-HSR was 6.96% (3.31% during the first-day DPT, and 3.65% during extended-day DPT). Approximately half of the positive reactions during extended-day DPT occurred during the second/third day. The increased detected pool prevalence of confirmed BL-HSR yielded by extended-day DPT was 0.03 (95% CI, 0.02%-0.04%; I 2  = 57.69%; P < .001), and the risk ratio of positive reactions between extended-day and single-day DPT was 1.94 (95% CI, 1.62-2.33; I 2  = 36.26%; P < .001). The risk difference increased per 1% increase in prevalence of BL-HSR by 0.6% (95% CI, 0.4%-0.7%; P < .001). Twenty-three severe reactions occurred during DPT, and only 2 severe reactions (0.02%) occurred during extended-day DPT. An additional 28 extended-day DPTs were needed to identify 1 mild reaction., Conclusions: The increased prevalence of confirmed BL-HSR observed during extended-day DPT could be attributed to the first-day DPT. As a result, our findings do not conclusively support the use of extended-day DPT over single-day DPT. Further studies, incorporating a washout period, are required to comprehensively compare these 2 approaches., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Eosinophilia is a challenge to our everyday clinical practice. There are multiple causes to consider when diagnosing eosinophilia, and drug hypersensitivity must be taken into account. It is especially difficult to manage it in hospitalized patients with multiple complications and infections. Allergy tests are not always as helpful as we would like, so we rely on clinical observation and laboratory analysis to establish our diagnosis. We present a unique clinical case because the same patient presented two clinical episodes of eosinophilia after the administration of Carbapenems in the context of abdominal infection.

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.

Local anesthetics (LAs) are commonly used in all medical specialties, particularly in association with surgery, obstetrics, dentistry, and emergency departments. Most individuals, starting from young children, are exposed to LAs during life. LA hardly induces adverse events when used in recommended doses and with proper injection techniques. However, immediate anaphylactic reactions to LA injections may be a rare but life-threatening manifestation. A comprehensive report of the event and performing a specialist examination are crucial to prevent further episodes. The diagnosis should be based on history, medical records, skin and challenge tests.

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.

Background: Most hospitals use electronic health records (EHR) to warn health care professionals of drug hypersensitivity (DH) and other allergies. Indiscriminate recording of patient self-reported allergies may bloat the alert system, leading to unjustified avoidances and increases in health costs. The aim of our study was to analyze hypersensitivities documented in EHR of patients at Lausanne University Hospital (CHUV)., Methods: We conducted a retrospective study on patients admitted at least 24 h to CHUV between 2011 and 2021. After ethical clearance, we obtained anonymized data. Because culprit allergen could be either manually recorded or selected through a list, data was harmonized using a reference allergy database before undergoing statistical analysis., Results: Of 192,444 patients, 16% had at least one allergy referenced. DH constituted 60% of all allergy alerts, mainly beta-lactam antibiotics (BLA) (30%), NSAID (11%) and iodinated contrast media (ICM) (7%). Median age at first hospitalization and hospitalization length were higher in the allergy group. Female to male ratio was 2:1 in the allergic group. Reactions were limited to the skin in half of patients, and consistent with anaphylaxis in 6%. In those deemed allergic to BLA, culprit drug was specified in 19%, 'allergy to penicillin' otherwise. It was impossible to distinguish DH based on history alone or resulting from specialized work-up., Conclusions: Older age, longer hospital stays, and female sex increase the odds of in-patient allergy documentation. Regarding DH, BLA were referenced in 4% of inpatient records. Specific delabeling programs should be implemented to increase data reliability and patient safety., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter NSAIDs for the treatment of a variety of inflammatory conditions. Urticaria is the most commonly reported immediate cutaneous clinical sign of HR-NSAIDs, but it can be a manifestation of pathophysiologically different clinical entities that require different therapeutic strategies. The aim of this study is to ease the identification of the correct phenotype of HR-NSAIDs in patients reporting urticaria associated with the intake of NSAIDs and provide updated information about their diagnosis and management., Methods: The study is a narrative review conducted by collecting the most relevant and up-todate data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity reactions. PubMed and Embase scientific databases were used as search engines to select relevant articles., Results: Patients developing HR-NSAIDs can be divided into two categories: selective responders (SR), who develop reactions after the administration of a single specific NSAID due to an underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical pathways related with prostaglandin metabolism, independently from an underlying immunological mechanism. Five major different categories of HR-NSAIDs have been identified: NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDsexacerbated respiratory disease (NERD), which are developed by CI patients, and single NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDsinduced delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and therefore are not routinely used in clinical practice. The management in SR patients consists of strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed., Conclusion: HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly based on a thorough clinical history and confirmed by a drug challenge test. Clinical management is based on strict avoidance and use of alternative tolerated medications. Overall, all therapeutic decisions depend on the correct identification of the type of reaction the patient experienced., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Cephalosporins, β-lactam antibiotics, commonly cause allergic reactions., Objective: To assess the clinical characteristics and management of pediatric patients with suspected cephalosporin allergy using direct graded oral challenges (GOCs)., Methods: Children referred for suspected cephalosporin allergy at 4 Canadian clinics were recruited over 10 years. Data on demographics, clinical reaction characteristics, and management were collected through a questionnaire. Patients underwent a direct GOC (initially 10% of the treatment dose, then 90% after 20 min), and reactions were monitored 1 week postchallenge. Families were contacted annually for up to 5 years to detect subsequent antibiotic reactions. Logistic regression analysis identified factors associated with positive GOC reactions., Results: Among the 136 patients reporting cephalosporin allergy, 75 (55.1%) were males with a median age of 3.9 years (interquartile range 2.3-8.7). Cefprozil represented the most common cephalosporin linked to the index reaction (67.6% of cases). Of the 136 direct GOCs, 5.1% had an immediate and 4.4% a nonimmediate reaction, respectively. Positive GOCs conducted in children with a history of skin-limited nonsevere rashes were classified as mild, benign skin rashes. Positive GOCs were more likely in children with food allergies (adjusted odds ratio 1.14; 95% confidence interval [95% CI] 1.00-1.29)., Conclusions: Direct GOCs are safe and effective for diagnosing pediatric cases that report nonvesicular skin-limited symptoms while being treated with cephalosporins., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Penicillin allergy is common, and there is increased clinician interest in direct oral challenge (DOC) as a testing strategy for low-risk penicillin allergy. To aid wider implementation of DOC, consensus definitions of low-risk penicillin allergy phenotypes, and standardized approaches to assessment, DOC procedures, and evaluation, are required., Areas Covered: This review systematically reviews studies that have utilized penicillin DOC in healthcare settings to identify heterogeneity in implementation approaches and synthesize low-risk definitions, procedures, and evaluation., Expert Opinion: Opportunity exists to standardize penicillin DOC procedures in patients with a low-risk penicillin allergy to optimize antimicrobial prescribing and reduce the burden of penicillin allergy. Standardizing the definitions of 'low-risk' and 'positive challenge,' and improving the evaluation of patient safety, alongside the development of a unified approach to the structure of undertaking an oral challenge, is likely to increase uptake and confidence among non-allergist clinicians.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 β-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/10 6 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., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Skin tests are one of the most widely used diagnostic tools for suspected drug allergies in children. Studies on systemic reactions occurring during skin testing with allergens have mostly been conducted in pediatric and adult patient groups together. However, data on adverse reactions including allergic reactions after drug skin tests in children are scarce. It is aimed to determine the adverse reactions after skin test in children with suspected drug allergy., Methods: Patients who underwent a drug skin test due to the suspicion of drug allergy between May 2017 and June 2020 were evaluated, retrospectively. Data about adverse reactions seen after skin testing at the testing area in the clinic were analyzed., Results: The study included 1,073 children (585 [54.5%] boys and 488 [45.5%] girls) with a median age of 7.5 years. A total of 12 (1.1%) reactions were detected after skin testing, and 4 (0.4%) of them were allergic reactions. Of the allergic reactions, three were anaphylaxis and one was urticaria. Two of the reactions (1 anaphylaxis and 1 urticaria) were detected after the skin prick test and the remaining 2 were detected after intradermal test. Three of the nonallergic reactions were considered as vasovagal reactions and seven were considered as nonspecific and anxiety-related reactions., Conclusion: Although drug skin tests were generally well-tolerated and adverse reactions were rare, severe allergic reactions including anaphylaxis may ensue. Skin tests should be necessarily performed in clinical settings in experienced centers., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objectives: Identifying instances where medications have been discontinued due to an adverse/allergic reaction however the patients' allergy status has not been updated appropriately. Data were evaluated in an established electronic prescribing and medicines administration system within a medium-sized teaching hospital., Methods: Details of all medications stopped due to allergic reaction over a 3-year period were extracted from the electronic prescribing system. The instances where the discontinued medication was not included in the patients' allergy status were investigated further. Patient records were explored to determine whether genuine reactions had occurred., Results: 434 medications were discontinued due to drug allergy over the time period. Of these, 26 cases were identified where a documented drug reaction had not been added to the patients' inpatient allergy history., Conclusions: Electronic systems provide a wealth of information which can be analysed to identify gaps in processes and systems. This information can be leveraged to improve these systems and subsequently improve patient safety., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Although rare, systemic hypersensitivity reactions to nedaplatin chemotherapy arise rapidly and can be life-threatening. The causes are unclear, and multiple potential mechanisms exist. Here, we report a case of systemic hypersensitivity reaction to nedaplatin and review the literature to establish a recommended protocol., Patient Concerns: A 62-year-old man was being treated for squamous lung cancer with multiple metastases. On the first day of chemotherapy, 5 minutes after nedaplatin infusion, he developed panic, shortness of breath, and dyspnea with rapid heart rate, reduced oxygen saturation, and elevated blood pressure., Diagnoses: The symptoms indicated that the patient had developed a severe hypersensitivity reaction to nedaplatin, which could be life-threatening without immediate intervention., Intervention: Nedaplatin was discontinued, and he was treated with oxygen, ECG monitoring, finger pulse oximeter monitoring, 10 mg dexamethasone sodium phosphate injected intravenously, 20 mg diphenhydramine hydrochloride injected intramuscularly, and 40 mg methylprednisolone sodium succinate injected intravenously., Outcome: His allergic symptoms resolved, and once his vital signs stabilized, he was given 5 mg oral desloratadine once daily and 10 mg oral ebastine once daily to alleviate the effects of the allergic reaction. Once his vital signs remained stable without any special supportive treatment, he was discharged from the hospital. His chemotherapy regimen was discontinued, with no plan for a follow-up treatment due to the possibility of cross-allergic reactions between platinum-based drugs., Lessons: Clinical use of nedaplatin should be monitored and managed intensively for prevention and treatment of hypersensitivity reactions. Care should be taken to control the titration rate during infusion while closely monitoring vital signs. Clinical staff should be prepared to treat allergic symptoms as soon as they appear. The acute phase should involve immediate discontinuation of the drug; intravenous saline infusion for volume expansion; rapid assessment of circulation, airway, respiration, state of consciousness, and skin condition; and administration of oxygen, antihistamines, and epinephrine as appropriate for anaphylaxis. More randomized clinical trials are needed to elucidate appropriate preventative and management strategies to improve patient safety and support their successful completion of clinical treatment programs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Sulfonamides, which are drugs commonly prescribed in hospital and outpatient settings, have historically been associated with a high incidence of hypersensitivity reactions. It is believed that there is an increased risk of cross-reactions with other drugs that contain this functional group in their structure. However, it has not been conclusively established that the sulfonamide group is the sole cause of hypersensitivity reactions, as non-antibiotic sulfonamides do not share the same accessory groups with antibiotic sulfonamides. Therefore, cross-reactivity between different types of sulfonamides and sulfonamide-type antibiotics is not clearly demonstrated, and allergic reactions may involve other mechanisms. Misinformation about this topic can lead to inappropriate use of alternative antibiotics with lower efficacy or higher adverse effects, contributing to antibiotic resistance. It is crucial to individualize and monitor patients with a history of allergies to sulfonamide-type antibiotics when introducing a new drug containing sulfa and manage any adverse reactions promptly. Desensitization protocols may be a viable option for patients who specifically benefit from these antibiotics, particularly those who are immunosuppressed. This article provides a descriptive bibliographic review to update information on sulfa allergy, its prevalence, management, and recommendations to prevent such reactions and optimize pharmacotherapy, without underusing these drugs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To assess the effects of patient variables, examination variables, and seasonality on allergic-like and physiologic reactions to iodinated contrast material (ICM)., Patients and Methods: All ICM-enhanced computed tomography (CT) examinations performed from June 1, 2009, to May 9, 2017, at our institution were included. Reactions were identified and categorized as allergic-like or physiologic and mild, moderate, or severe. The effect of patient and examination variables on reactions was evaluated by logistic regression models., Results: A total of 359,977 CT examinations performed on 176,886 unique patients were included. A total of 1150 allergic-like reactions (0.32%; 19 severe [0.005%]) and 679 physiologic reactions (0.19%; 3 severe [0.0008%]) occurred. On multivariable analysis, iopromide had higher rates of reactions compared with iohexol (allergic-like reactions: odds ratio [OR], 3.07 [95% CI, 2.37 to 3.98], P<.0001; physiologic reactions: OR, 2.60 [1.92 to 3.52], P<.0001). Non-White patients had higher rates of reactions compared with White patients (allergic-like reactions: OR, 1.77 [1.36-2.30], P<.0001; physiologic reactions: OR, 1.76 [1.27-2.42], P=.0006). Patient age, sex, prior ICM reaction, ICM dose, CT location, and CT type were also significantly associated with reactions. No significant seasonality trend was observed (P=.07 and .80)., Conclusion: Non-White patients and patients administered iopromide had higher rates of acute reactions compared with White patients and patients administered iohexol. Younger patients (<50 years vs 51 to 60 years), female sex, history of ICM allergy or other allergies, ICM dose, and contrast-enhanced CT location and type also correlated with higher acute reaction rates., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Furazolidone is a nitrofuran antimicrobial agent used in the treatment of bacterial and protozoal infections. Hypersensitivity to furazolidone is rarely reported and only eight cases have been documented in English since 1967., Objectives: To report a 24-year-old man who developed exanthematous drug eruptions in general and swelling sensation of the hands after first dose of oral administration of medicines for Helicobacter pylori infection 7 h later, who was finally confirmed with delayed-type IV allergic reaction to furazolidone by provocation tests. And to review the existing literature., Methods: Thorough clinical examination, prick, intradermal, and patch tests, drug provocation tests were performed in the patient., Results: Skin tests of all used drugs were negative. Drug provocation tests to furazolidone resulted to be positive., Conclusions: Clinicians should be aware that furazolidone may induce delayed-type allergic reactions; diagnostic approaches should be taken to identify the responsible drug when multiple medications were used concurrently., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Ibuprofen and other arylpropionic acid derivatives (APs) are among the most consumed nonsteroidal anti-inflammatory drugs worldwide at all age ranges; however, little is known about drug hypersensitivity reactions (DHRs) they induce., Objective: To characterize in detail patients reporting DHRs to APs., Methods: We prospectively evaluated patients with symptoms suggestive of AP-DHRs and analyzed their clinical characteristics, reported reactions, and diagnostic approaches., Results: Six hundred sixty-two patients confirmed as hypersensitive to APs were included: 489 with cross-reactive reactions (CRs) (73.86%) and 173 with selective reactions (SRs) (26.13%). The percentage of subjects reporting reactions to ibuprofen and dexketoprofen was higher in CRs (P = .005 and P = .01, respectively), whereas naproxen and ketoprofen were more frequently involved in SRs (P = .0002 and P = .00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria, combined or not with angioedema in both CRs and SRs. The result of nasal provocation test with lysine acetylsalicylate was positive in 156 cases (77.14% in patients showing exclusively respiratory symptoms, and in 68.18% of those with both cutaneous and respiratory involvement). To confirm diagnosis, drug provocation test with acetylsalicylic acid was required in 246 CR patients (50.3%), whereas in 28 SR patients (16.18%) drug provocation test with the culprit AP was required., Conclusions: Skin is the organ most commonly involved in AP-DHRs, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are necessary to clarify the underlying mechanism in DHRs induced by APs., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Penicillin allergy is the most common drug allergy in the US population. A penicillin allergy label is associated with poor patient outcomes including increased hospital length of stay, increased perioperative infections, and overall increased mortality. A penicillin allergy evaluation accurately identifies approximately 9 of 10 patients who, despite reporting a history of penicillin allergy, can receive penicillins safely. Penicillin allergy evaluations should be offered proactively to healthy patients during routine visits, including children and pregnant women, in advance of antibiotic need., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chlorhexidine and clindamycin, especially the latter, rarely cause anaphylaxis., Objective: To report a rare case of chlorhexidine- and clindamycin-induced anaphylaxis., Methods: Case report., Results: A 21-year-old female experienced anaphylaxis after receiving intravenous clindamycin after a left big toe fracture fixation operation; she also had a similar reaction after using a mouthwash. Therefore, we suspected the culprit might be chlorhexidine, and the skin prick and serum specific IgE test results confirmed our suspicion. Then the clindamycin provocation test verified that the patient also had hypersensitivity to clindamycin. However, the allergy tests for penicillin and cefuroxime were negative., Conclusions: Only four cases of clindamycin-induced anaphylaxis have been reported, and this is the first report of clindamycin-induced anaphylaxis verified by provocation test. The patient was given clindamycin because she was incorrectly labeled as having penicillin and cephalosporin allergies during the routine allergy test. It is essential to address this problem in China.

Background: Immediate hypersensitivity reactions (IHRs) are commonly found in patients receiving paclitaxel. Effects of paclitaxel vary because of variable co-therapy or re-challenge with paclitaxel., Objective: Our objective was to investigate the incidence, patterns, and risk factors for paclitaxel-related IHRs and management of IHRs in gynecologic malignancy patients., Methods: This retrospective study was performed in gynecologic cancer patients receiving paclitaxel-based regimens at Siriraj hospital from January 2012 to December 2017., Results: 416 subjects were included and received ranitidine 50 mg, dexamethasone 20 mg, ondansetron 16 mg intravenously and diphenhydramine 50 mg orally 30 minutes before starting chemotherapy. The incidence of IHRs was 17.79%. IHRs occurring on first exposure to paclitaxel was 81.1% and occurred within 30 minutes after starting paclitaxel. The most commonly found presentation of IHRs were skin reactions (86.5%). In multivariate analysis, age < 54.5 years, stage of cancer < 2, and leukocyte cell count < 7.735 × 109/L were significantly associated with IHRs. Seventy-two out of 74 patients that recovered from IHRs were reintroduced paclitaxel. Forty-seven patients (97.92%) of 48 patients with mild reactions were successfully reintroduced to paclitaxel after treatment with chlorpheniramine or other interventions., Conclusions: The incidence of paclitaxel-related IHRs was about one in five. Skin reactions were the most commonly occurring reactions. Younger age, stage of cancer < 2, and leukocytes < 7.735 × 109/L were significant risk factors for IHRs. Patients with IHRs recovered without the use of dexamethasone and antihistamines before the reintroduction of paclitaxel.

Background: There is no accepted grading system classifying the severity of immediate reactions to drugs., Objective: The purpose of this article is to present a proposed grading system developed through the consensus of drug allergy experts from the United States Drug Allergy Registry (USDAR) Consortium., Methods: The USDAR investigators sought to develop a consensus severity grading system for immediate drug reactions that is applicable to clinical care and research., Results: The USDAR grading scale scores severity levels on a scale of 0 to 4. A grade of no reaction (NR) is used for patients who undergo challenge without any symptoms or signs, and it would confirm a negative challenge result. A grade 0 reaction is indicative of primarily subjective complaints that are commonly seen with both historical drug reactions and during drug challenges, and it would suggest a low likelihood of a true drug allergic reaction. Grades 1 to 4 meet the criteria for a positive challenge result and may be considered indicative of a drug allergy. Grade 1 reactions are suggestive of a potential immediate drug reaction with mild symptoms. Grade 2 reactions are more likely to be immediate drug reactions of moderate severity. Grade 3 reactions have features suggestive of a severe allergic reaction, whereas grade 4 reactions are life-threatening reactions such as anaphylactic shock and fatal anaphylaxis., Conclusion: This proposed grading schema for immediate drug reactions improves on prior schemata by being developed specifically for immediate drug reactions and being easy to implement in clinical and research practice., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: On average about 10% of parents report hypersensitivity to at least 1 drug in their children. After diagnosis process a few of these reactions are being confirmed as drug hypersensitivity reactions. The aim of the study was to assess the real-life prevalence of drug hypersensitivity in children based on drug provocation tests., Material and Methods: The authors included 113 children, aged 4-18 years, referred to Pediatrics and Allergy Clinic in Łódź, Poland, due to incidence of adverse reaction during treatment. Medical history regarding allergies to drugs was taken in accordance to the form developed by the United States Food and Drug Administration Adverse Event Reporting System. Skin prick tests, intradermal test and drug provocation test were performed in all patients., Results: In all 113 patients suspected of drug allergy, after all diagnostic procedures, the authors proved IgE-mediated allergy to β-lactams, nonsteroid anti-inflammatory drugs, local anesthetics in 19 patients (16.8%). Previous history of allergy was a risk factor for drug allergy in studied patients (p = 0.001). The most frequent symptoms of allergy were urticaria and erythematous papular rash., Conclusions: Drug allergy is a difficult problem in the practice of a doctor and is difficult to diagnose, especially in the pediatric population. It seems that too often isolated symptoms reported during infection or disease are taken as a symptom of drug allergy, and not as a symptom resulting from the course of the disease. Int J Occup Med Environ Health. 2023;36(5):632-42., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Background/aim: Data on the prevalence of allergic diseases in children with proven drug allergies are limited. We aim to evaluate the frequency of allergic comorbidity in children with proven common drug allergies., Materials and Methods: Children with drug hypersensitivity confirmed by diagnostic allergy tests at our center between January 2010 and December 2020 were screened retrospectively. Patients with the most common drug allergies (due to antibiotics, nonsteroidal antiinflammatory drugs [NSAIDs], and antiepileptic drugs) were selected for analysis. Age, sex, the culprit drug, initial reaction characteristics, diagnostic test results, and the study physician who diagnosed concomitant allergic diseases were noted., Results: A total of 168 patients (boys, 51.2%) with a median age of 12 years (IQR = 8-16.3) were included in the study. The culprit drug was an antibiotic in 63% (n = 106), NSAID in 25% (n = 42) and anticonvulsant in 11.9 % (n = 20) of the patients. Drug hypersensitivity reactions were immediate in 74.4 % (n = 125) and delayed in 25.6 % (n = 43) of the patients. Seventy-five patients (44.6 %) had at least one allergic disease, most commonly rhinitis (27.3 %, n = 46) or asthma (25 %, n = 42). Fifty-five patients underwent skin prick tests with aeroallergens, producing a positive result in 60% (n = 31). The prevalence of allergic disease was not differing according to the culprit drug. The frequency of developing at least one concomitant allergic disease was 47.2% (n = 50/106) for antibiotic hypersensitivity, 52.4% (n = 22/42) for NSAID hypersensitivity, and 15% (n = 3/20) for anticonvulsant hypersensitivity (p < 0.00).Immediate drug hypersensitivity reactions were more frequent in children who had allergic diseases (80 % vs. 64.5 %; p = 0.027)., Conclusion: Nearly half (44.6%) of the children with proven drug hypersensitivity had concomitant allergic diseases and immediate reactions were more common in this group. Children evaluated for drug hypersensitivity should be assessed for other allergic diseases., (© TÜBİTAK.)

Background: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients., Objectives: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative., Methods: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative., Results: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it., Conclusions: In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Inaccurate penicillin allergy labels may be delabelled following evaluation. The intervention in this study was an email-based notification system regarding the appropriateness for penicillin allergy evaluation, with a view to delabelling, as identified by a deep learning artificial intelligence algorithm. Of the intervention group (n = 59), three (5.1%) individuals had their penicillin allergies delabelled, which was significantly more than the control group (0%, P = 0.002). Further research to optimise such approaches is required., (© 2023 Royal Australasian College of Physicians.)

Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H567 ).

Purpose of Review: As a sulfone antibacterial agent, dapsone has been widely used to treat leprosy. Moreover, dapsone is also used in many immune diseases such as herpetic dermatitis because of its anti-inflammatory and immunomodulatory effects. However, dapsone can cause several adverse effects, the most serious being dapsone hypersensitivity syndrome. Dapsone hypersensitivity syndrome is characterized by a triad of eruptions, fever, and organ involvement, which limits the application of dapsone to some extent., Recent Findings: In this article, we review current research about the interaction model between HLA-B*13:01, dapsone, and specific TCR in dapsone-induced drug hypersensitivity. In addition to the proposed mechanisms, we also discussed clinical features, treatment progress, prevalence, and prevention of dapsone hypersensitivity syndrome. These studies reveal the pathogenesis, clinical features, and prevalence from the perspectives of genetic susceptibility and innate and adaptive immunity in dapsone hypersensitivity syndrome, thereby guiding clinicians on how to diagnose, prevent, and treat dapsone hypersensitivity syndrome., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There is a lack of understanding of the barriers reported by healthcare providers when evaluating beta-lactam allergies, but knowledge of these barriers is required for practical and effective implementation interventions., Methods: Twenty-five healthcare providers, consisting of physicians, nurses and pharmacists practicing in the areas of intensive care, emergency medicine, infectious disease and general hospital practice, were interviewed between September 2021 and July 2023. Twenty-three of these providers were practising in the USA. A semi-structured interview guide grounded in the Theoretical Domain Framework was used for the interviews. Deductive and inductive analysis was performed on the interview transcripts, and translated into intervention recommendations using the Behaviour Change Wheel., Results: Widely held beliefs included a lack of clear policy for the evaluation of allergies, confusing or missing documentation of allergy information, confidence in their own and their colleagues' ability to evaluate allergies when information is available, and pharmacists as the provider most equipped to evaluate beta-lactam allergies., Conclusions: Health systems should adopt and disseminate policies for the evaluation of beta-lactam allergies, and promote the use of pharmacists in the evaluation of drug allergies when possible. Allergy sections of electronic health records should be reworked to encourage unambiguous documentation of allergy reactions and support using previously tolerated beta-lactam antibiotics., (Copyright © 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

In the United States, approximately 27 million people have a documented penicillin allergy, but 90% of the allergies are falsely labeled. By rechallenging suspected allergies, a pharmacist can optimize patient care, fulfill antimicrobial stewardship objectives, and educate patients on true allergies. We suggest a protocol that allows pharmacists to investigate the presence of an allergy and conduct a challenge when indicated. The protocol consists of a patient interview, a risk assessment, an oral rechallenge, and the potential for a skin test. The testing and delabeling of penicillin allergies will enhance the practice of antimicrobial stewardship in the outpatient setting. In the changing landscape of pharmacy, community pharmacists can increase their services and improve patient care. Owing to limited documented experience in the outpatient pharmacy, an opportunity to set the standard and be a leader in the field is present., (Copyright © 2023 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Older adults have an increased risk of adverse drug reactions and negative effects associated with alternative antibiotic use. Although the number of antibiotic allergies reported increases with age, the characteristics and outcomes of older adults receiving drug allergy assessment are unknown., Objective: To assess the characteristics and outcomes of drug allergy evaluations in older adults., Methods: We considered patients aged above or equal to 65 years enrolled in the United States Drug Allergy Registry (USDAR), a US multisite prospective cohort (January 16, 2019 to February 28, 2022). Data were summarized using descriptive statistics., Results: Of 1678 USDAR participants from 5 sites, 406 older adults aged above or equal to 65 years (37% 65-69 years, 37% 70-74 years, 16% 75-79 years, and 10% ≥80 years) received 501 drug allergy assessments. USDAR older adults were primarily of female sex (69%), White (94%), and non-Hispanic (98%). Most USDAR older adults reported less than or equal to 1 infections per year (64%) and rated their general health as good, very good, or excellent (80%). Of 296 (59%) penicillin allergy assessments in USDAR older adults, 286 (97%) were disproved. Other drug allergy assessments included sulfonamide (n = 41, 88% disproved) and cephalosporin (n = 20, 95% disproved) antibiotics. All 41 drug allergy labels in USDAR participants aged above or equal to 80 years and all 80 penicillin allergy labels in USDAR men aged above or equal to 65 years were disproved., Conclusion: Older adults represented a quarter of USDAR participants but were neither racially nor ethnically diverse and were generally healthy without considerable antibiotic need. Most older adults presented for antibiotic allergy assessments, the vast majority of which were disproved. Drug allergy assessments may be underutilized in the older adults who are most vulnerable to the harms of unconfirmed antibiotic allergy labels., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Many systemic medications have been observed to cause ocular toxicity. A subset of these reactions is thought to involve immunomodulation or a hypersensitivity reaction. As new medications are developed, ocular adverse effects are becoming increasingly prevalent. Herein we review immune-mediated drug reactions affecting they eye with special attention to the hypersensitivity mechanisms leading to ocular toxicity., Recent Findings: Recent work has focused on mechanisms and risk of immune-mediated ocular adverse drug reactions including genetic susceptibility and loss of ocular immune privilege., Summary: Given the consequences of immune-mediated ocular adverse drug reactions, clinicians must be aware of these to facilitate early recognition and management. The prompt involvement of an ophthalmologist for diagnosis and management is often essential to preserve vision and avoid long-term morbidity., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)