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UNASSIGNED: This report presents a case of pseudoephedrine-induced nonpigmented bullous fixed drug eruption (NBFDE) manifesting as recurrent palmoplantar exfoliation in a scuba diver. It emphasizes the importance of considering drug allergies in the differential diagnosis when divers present with peeling hands and soles.
UNASSIGNED: A 38-year-old female scuba diver experiencing recurrent palmoplantar exfoliation underwent a clinical evaluation, patch testing, an interferon-gamma enzyme-linked immunospot (ELISpot) assay, and graded drug challenges with pseudoephedrine and phenylephrine.
UNASSIGNED: Patch testing yielded negative results; however, the ELISpot assay indicated a strong immune response to pseudoephedrine. A graded challenge involving pseudoephedrine successfully reproduced the symptoms, confirming a diagnosis of pseudoephedrine-induced NBFDE. Subsequently, a challenge with phenylephrine elicited a milder reaction, suggesting it as a potential alternative medication for the patient.
UNASSIGNED: This case highlights NBFDE as a potential cause of skin peeling in scuba divers who are allergic to pseudoephedrine. It emphasizes the importance of considering drug allergies when diagnosing palmoplantar exfoliation in divers and underscores the need for a thorough evaluation of medication use in this group. Alternative medications and management strategies should be considered for divers with a pseudoephedrine allergy to prevent ear barotrauma while minimizing the risk of adverse skin reactions.

BACKGROUND: Vancomycin infusion reaction (VIR), reportedly mediated through Mas-Related G Protein-Coupled Receptor-X2 (MRGPRX2), is the primary vancomycin-induced immediate drug reaction (IDR). Clinically, distinguishing the underlying drug-induced IDR mechanisms is crucial for future treatment strategies, including drug restriction, re-administration, and pretreatment considerations. However, the lack of validated diagnostic tests makes this challenging, often leading to unnecessary drug restriction.
OBJECTIVE: To determine if intradermal tests (IDTs) and, separately, the basophil activation test (BAT) differentiate VIR from vancomycin-tolerant subjects.
METHODS: Cross-sectional study of vancomycin-exposed adults with and without a history of VIR. Demographics, allergy-related comorbidities, history of vancomycin exposures, and VIR characteristics were collected. IDT with vancomycin was performed. IDT dose responses EC50, IDT-related local symptoms, and BAT were compared between groups.
RESULTS: 11 VIR and 10 vancomycin-tolerant subjects were enrolled. The most reported VIR symptoms were pruritus (82%), flushing (82%), hives (46%), hives (46%), angioedema (27%), and dyspnea (19%). The IDT dose response mean EC50 was 328 μg/mL (95% CI 296, 367) in the VIR vs. 1,166 μg/mL (95% CI 1029, 1379) in the tolerant group (p<0.0001). All VIR subjects reported IDT-related local pruritus compared to 60% of tolerant subjects (p=0.0185). The %CD63+ basophils were consistently <2%, without significant differences between groups (p < 0.54).
CONCLUSIONS: Variations in skin test methodologies could help identify other IDR mechanisms beyond IgE. This skin test protocol holds the potential for identifying VIR, particularly in cases where patients have received multiple drugs while BAT is insufficient. Future studies will validate and delineate its predictive value, assessing the risk of VIR.

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.

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Cephalosporin antibiotics are widely used in clinical settings, but they can cause hypersensitivity reactions, which may be influenced by genetic factors such as the expression of Human leukocyte antigen (HLA) molecules. This study aimed to investigate whether specific HLA alleles were associated with an increased risk of adverse reactions to cephalosporins among individuals in the Taiwanese population. This retrospective case-control study analyzed data from the Taiwan Precision Medicine Initiative (TPMI) on 27,933 individuals who received cephalosporin exposure and had HLA allele genotyping information available. Using logistic regression analyses, we examined the associations between HLA genotypes, comorbidities, allergy risk, and severity. Among the study population, 278 individuals had cephalosporin allergy and 2780 were in the control group. Our results indicated that certain HLA alleles, including HLA-B*55:02 (OR = 1.76, 95% CI 1.18-2.61, p = 0.005), HLA-C*01:02 (OR = 1.36, 95% CI 1.05-1.77, p = 0.018), and HLA-DQB1*06:09 (OR = 2.58, 95% CI 1.62-4.12, p < 0.001), were significantly associated with an increased risk of cephalosporin allergy reactions. Additionally, the HLA-C*01:02 allele genotype was significantly associated with a higher risk of severe allergy (OR = 2.33, 95% CI 1.05-5.15, p = 0.04). This study identified significant associations between HLA alleles and an increased risk of cephalosporin allergy, which can aid in early detection and prediction of adverse drug reactions to cephalosporins. Furthermore, our study highlights the importance of HLA typing in drug safety and expanding our knowledge of drug hypersensitivity syndromes.

We describe a rare case of a 54-year-old female with hairy cell leukemia, who following treatment for neutropenic sepsis, developed an extensive severe maculopapular exanthema with perifollicular hemorrhage. Cladribine, cotrimoxazole, allopurinol, domperidone, amikacin, piperacillin/tazobactam, and meropenem had all been given in the 9 days prior to eruption onset. Three months later, drug patch testing/delayed intradermal testing was positive to cotrimoxazole, trimethoprim, amikacin, piperacillin/tazobactam, and meropenem, with additional evidence of penicillin cross-reactivity. Drug challenge tests were negative to allopurinol and domperidone. She was diagnosed with multiple drug hypersensitivity to cotrimoxazole, amikacin, piperacillin/tazobactam, and meropenem. Multiple drug hypersensitivity is a novel syndrome mainly seen with severe delayed type IV drug eruptions, involving long-lasting strong T-cell reactivity to two or more structurally unrelated drugs.

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.

CONCLUSIONS: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
OBJECTIVE: Penicillin allergy documentation in the electronic health record (EHR) lacks detail with regard to type of reaction, history of reaction, and other tolerated β-lactams. Because of concern for penicillin allergy cross-reactivity with cefazolin, patients with a reported penicillin allergy are frequently prescribed suboptimal preoperative antibiotics, which have been associated with negative patient outcomes, including increased risk of surgical site infection. The purpose of this study was to increase preoperative use of cefazolin via improvement to the documentation of penicillin allergies in the EHR.
METHODS: This single-center, quasi-experimental quality improvement study compared patients with a self-reported penicillin allergy admitted for select elective surgeries before and after implementation of a penicillin allergy questionnaire. The primary outcome was receipt of cefazolin for surgical prophylaxis. Secondary outcomes were the proportion of patients with detailed penicillin allergy documentation, the proportion of patients with surgical site infections occurring within 30 days of surgery, and the proportion of patients who received the full antibiotic dose before the first surgical incision.
RESULTS: A total of 100 patients were included in the preintervention group, while 85 patients were included in the postintervention group. Cefazolin use was higher in the postintervention group (13.0% vs 41.2%; P < 0.001). The postintervention group also had a larger proportion of patients with detailed allergy documentation (2.0% vs 50.6%; P < 0.001) and who received the full preoperative antibiotic dose before the first incision (25.0% vs 48.2%; P = 0.001). There was no statistical difference between the groups in the incidence of surgical site infection at 30 days after surgery (3.0% vs 1.2%; P = 0.63).
CONCLUSIONS: Preoperative cefazolin use was higher in patients with a reported penicillin allergy after implementation of a penicillin allergy questionnaire and EHR documentation tool.

BACKGROUND: Kounis syndrome is defined as a combination of acute coronary syndrome and allergic reactions.
OBJECTIVE: In this review, we aim to describe the etiological, clinical, and diagnostic characteristics of Kounis syndrome.
METHODS: A literature search using PubMed was conducted for the past 32 years using keywords, resulting in the selection of 761 scientific papers. From these, 217 articles describing 235 clinical cases were selected. Patients under 18 years of age or without a confirmed diagnosis were excluded.
RESULTS: Among the 235 patients, type I Kounis syndrome was observed in 49.7%, type II in 27.2%, type III in 5.9%, and a combination of types I and II in 1.0%; in 16.2%, it was not possible to classify the type of Kounis syndrome. The median age was 57 years, and 68.5% of the patients were male. The most common causes were antibiotics (32.3%) and non-steroidal anti-inflammatory drugs (24.3%). The clinical features included chest pain (59.1%), hypotension (74.2%), itching (30.6%), and dyspnea (30.6%). Electrocardiographic monitoring revealed ST-segment elevation in 42.9% and was normal in only 5.5% of patients. Coronary angiography was performed in 80.4% of the patients, revealing unchanged coronary arteries in 50.3% of cases. Сonclusion: Allergic myocardial infarction is a serious complication of drug therapy.