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Purpose 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). Conclusion Preoperative cefazolin use was higher in patients with a reported penicillin allergy after implementation of a penicillin allergy questionnaire and EHR documentation tool. [ABSTRACT FROM AUTHOR]

Drug reactions with eosinophilia and systemic symptoms (DRESS) and Stevens‐Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse hypersensitivity reactions with distinct clinical manifestations. Regulatory T (Treg) cells may behave differently in these syndromes, contributing to their diverse clinical features and outcomes. This study compared Treg dynamics between DRESS and SJS/TEN patients during the acute and recovery phases. Flow cytometry quantitatively analysed and defined the immunophenotype of CD4+CD25+CD127−FoxP3+ Tregs in blood from DRESS and SJS/TEN patients indicated that Treg percentages were lowest in DRESS patients during the acute phase compared to those in the recovery phase in DRESS patients and the acute phase in SJS/TEN patients. During the acute phase, CTLA‐4 expression in Tregs in both DRESS patients with and without autoimmune sequelae was significantly increased, while only DRESS patients without autoimmune sequelae had elevated OX40 expression compared to the healthy controls. High IL‐10 expression in Tregs during the acute phase in SJS/TEN patients was also observed. The suppressive function of Tregs was lower in DRESS compared to SJS/TEN, which was determined using a suppression assay by co‐culturing autologous Treg and effector T cells. Furthermore, NanoString technology explored mRNA profiles in Tregs. Genes associated with the JAK/STAT pathway were found to be downregulated during the acute phase in DRESS patients who later developed autoimmune sequelae. Our findings evidenced impaired Treg function in DRESS compared to SJS/TEN. The early disturbance of the JAK/STAT pathway may serve as a prognostic marker for autoimmune development in DRESS patients. [ABSTRACT FROM AUTHOR]

Background: Hypersensitivity reactions (HSR) are reported for the macrolides, lincosamides, and streptogramins (MLS) antibiotic family. Data about cross‐reactivity among and between MLS remain scarce or controversial. Objectives: The aim of this study was to provide an overview of hypersensitivity cross‐reactions among MLSs based on data extracted from the French National Pharmacovigilance Database (FPVD). Methods: Cases of HSR to MLSs reported between January 1985 and December 2019 were extracted from the FPVD using standardized MedDRA queries (SMQ). Cases including an allergological test involving multiple MLSs and giving at least one positive result were included. Results: Of the 8394 cases reviewed, 149 were included. HSR mainly involved pristinamycin (n = 83; 53.2%) and spiramycin (n = 31; 19.9%). HSR to MLS was immediate in 54 cases and delayed in 94 cases. Skin tests represented the majority of the allergological tests performed (n = 728; 84.7%), followed by reintroduction tests (n = 79; 9.2%). Eighty‐six cross‐reactivities among MLS were identified in 62 cases (41.6%). All the 25 explorations performed for streptogramins showed cross‐reactivities, but only 30/253 among macrolides (11.9%). Cross‐reactivities between the three MLS were observed in 31/322 (9.6%) of the allergological explorations. Conclusion: This study highlights the possibility of cross‐reactivity among and between MLSs. Dermatologists and allergologists managing patients with HSR to MLSs should be aware of a risk of cross‐reactivity among the macrolides and between the different classes of MLS and to perform MLSs allergological testing before recommending an alternative antibiotic, especially in severe drug hypersensitivity from the MLS family. [ABSTRACT FROM AUTHOR]

Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs. A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016–2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019–2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined. The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4–8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3–63.7; P = 0.001). The in vitro BAT showed higher activation of CD63+ basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P < 0.05). Only four patients (8.5%) with oxaliplatin-induced ADRs were positive for oxaliplatin-specific IgE. This study found that 26.0% of patients with oxaliplatin-induced ADRs could not undergo oxaliplatin rechallenge. HLA-DRB∗12:01 is regarded as a genetic marker for oxaliplatin-induced hypersensitivity. [ABSTRACT FROM AUTHOR]

This report presents a case of pseudoephedrine-induced non-pigmented 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. 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. 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. 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: Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs. Methods: A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016–2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019–2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined. Results: The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4–8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3–63.7; P = 0.001). The in vitro BAT showed higher activation of CD63+ basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P

Adverse drug reactions (ADRs) are closely associated with increased morbidity and mortality rates, prolonged hospitalization durations, and higher healthcare costs. This study aimed to estimate the incidence, clinical features, and reporting status of ADRs to improve the current ADR reporting system and prevent recurrent ADRs in hospitals. This retrospective study was conducted at a regional referral hospital. Patients diagnosed with ADRs over a 5-year period (2009-2014) were recruited for this study. An ADR was identified as an ADRrelated diagnosis in a patient’s medical record or an ADR registered through the inhospital ADR reporting system. The incidence, culprit drug, clinical manifestations, reporting source, severity, related management, and recurrence rate were assessed. Among 1,112 patients, 1,375 ADR events were collected, an estimated 0.06% of the total number of patient visits. Diagnostic contrast agents (46.4%) were the most common culprit drugs, followed by antibiotics (22.0%), nonsteroidal anti-inflammatory drugs (9.9%), and opioids (4.5%). Skin reactions (67.5%) such as rashes and hives were the most frequent manifestations. Additional ADR-related medical attention was necessary in two thirds of cases. One hundred eighty ADR events (13.1%) were categorized as severe, and 19 patients (1.4%) experienced re-exposure to the culprit drugs. Four patients (0.3%) experienced fatal ADRs. Physicians were the most frequent ADR reporters in the in-hospital ADR reporting system. In conclusion, many ADR events may be overlooked, and re-exposure to causative drugs commonly occurs. Continuous education and maintenance of a reporting system may be important for preventing recurrent ADRs.

Jomana W Alsulaiman,1 Khalid A Kheirallah,2 Ahmad Alrawashdeh,3 Tareq Saleh,4 Maha Obeidat,5 Yareen J Alawneh,2 Ziydoun Abu Sanad,5 Wajdi Amayreh,1 Rama J Alawneh2 1Department of Pediatrics, Faculty of Medicine, Yarmouk University, Irbid, Jordan; 2Department of Public Health and Family Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Allied Medical Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa, Jordan; 5Department of Pediatrics, Princess Rahma Teaching Hospital, Irbid, JordanCorrespondence: Jomana W Alsulaiman, Associate Professor of Pediatrics, Department of Pediatrics, Faculty of Medicine, Yarmouk University, Irbid, 21163, Jordan, Tel + 962 07 9941 2277, Email jomana.a@yu.edu.joBackground: Implementing allergy testing among children with a reported history of penicillin allergy could be challenging, particularly in developing countries with limited resources. This study screened and risk-stratified the likelihood of true penicillin allergy among children labeled with penicillin allergy in Jordan.Methods: A web-based survey, completed by parents, assessed history, type, and severity of penicillin allergic reactions, including age at diagnosis, symptoms, time to the reaction, reaction’s course and resolution, and received medical evaluation/testing. Low-risk allergic symptoms were defined as vomiting, diarrhea, headache, dizziness, itching, rash, cough, or runny nose without evidence of anaphylaxis or severe cutaneous reactions.Results: A total of 530 parents of “penicillin allergy”-labeled children completed the survey. Of these, 86.4% reported allergic reactions to penicillin and 13.6% reported avoidance of penicillin due to family history. Among the former, 52.2% were male, 67.3% were three years old or younger when the reported reaction was established, and 68.3% experienced exclusively low-risk symptoms. Overall, skin rash was the most reported symptom (86.0%). High-risk symptoms were reported in 31.5% of children. About two-thirds (64.0%) of children were reported to have experienced symptoms after the first exposure to penicillin. The most common indication for antibiotic use was a throat infection (63.8%). Asthma comorbidity was significantly higher among high-risk (24.8%) compared low-risk group (11.5%).Conclusion: In Jordan, many parent-reported penicillin allergic reactions seem to be clinically insignificant and unlikely to be verifiable, which can adversely affect patients’ care and antimicrobial stewardship. An appropriate clinical history/evaluation is a key step in identifying true immunoglobulin E-mediated allergic reactions and risk stratifying patients for either de-labeling those with obviously non‐immune–mediated reactions or identifying candidates for direct oral challenge test.Keywords: children, drug hypersensitivity, drug resistance, Jordan, penicillin resistance

Abstract Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity reaction characterized by cutaneous rash, lymphadenopathy, fever, eosinophilia, leukocytosis, and life-threatening organ dysfunctions. We describe the case of a 26 year old patient admitted to the Emergency Department for DRESS syndrome after sulfasalazine treatment for rheumatoid arthritis in the right knee. Whole body computer tomography showed multiple neck, chest, and abdominal lymphadenopathy with splenomegaly, massive ascites and severe hepatic cytolysis. Serology results for Epstein-Barr Virus (EBV), influenza, measles, rubella, hepatitis A and B were negative. The histologic analysis of skin, lymph node and bone marrow biopsies could not indicate a classical Hodgkin’s Disease or iatrogenic immunodeficiency/EBV-associated lymphoproliferative disorder (LPD), Hodgkin type. The relatively small caliber of the CD30 + immunoreactive blastoid cells in the lymph nodes suggested reactive immunoblasts rather than Hodgkin cells. The morphologic aspects of the lymph node biopsies with predominance of T-cells were compatible with the diagnosis of a sulfasalazine-induced DRESS syndrome as the patient had a high RegiSCAR score for DRESS. [DRESS Syndrome Foundation: Diagnosis and Treatment. (2023)] The patient’s complex clinical course, marked by two hospital admissions, highlights the challenges in diagnosing and managing DRESS. This case underscores the need for individualized care, close patient monitoring, and further research to better understand DRESS’s underlying mechanisms and optimal therapeutic strategies.

Background: Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies in a larger cohort of mastocytosis patients. We assessed prevalence, triggers and risk factors of HR in adults with mastocytosis in the ECNM registry. Methods: Data were collected in 27 ECNM centers. We analyzed potential triggers (Hymenoptera venoms, food, drug, inhalant and others) and risk factors at diagnosis and during follow‐up. The study group consisted of 2485 adults with mastocytosis, 1379 women (55.5%) and 1106 men (44.5%). Median age was 48.2 years (range 18–91 years). Results: Nine hundred and forty eight patients (38.1%) reported one or more HR'. Most common triggers were Hymenoptera venoms in cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), whereas in advanced SM (advSM), most common elicitors were drugs, including nonsteroidal anti‐inflammatory agents and penicillin. In multivariate analyses, tryptase level < 90 ng/mL, <15% infiltration by mast cells in bone marrow biopsy‐sections, and diagnosis of ISM were identified as independent risk factors for HR. For drug‐induced HR, prominent risk factors were advSM and high tryptase levels. New reactions were observed in 4.8% of all patients during 4 years follow‐up. Conclusions: HR are mainly triggered by Hymenoptera venoms in patients with CM and ISM and by drugs in patients with advSM. Tryptase levels <90 ng/mL, mast cell bone marrow infiltration <15%, and WHO category ISM are predictors of HR. New HR occur in 4.8% of all patients within 4 years. [ABSTRACT FROM AUTHOR]

Acute generalized exanthematous pustulosis (AGEP) is a sudden-onset, severe and rare adverse skin reaction characterized by nonfollicular sterile pustules tending to intertriginous localization. Lesions develop on erythematous and edematous skin. It is often triggered by drugs. This article presents a case diagnosed with AGEP due to etodolac. To the best of our knowledge, this is the second case of AGEP due to etodolac in the literature. A 47-year-old female patient presented with diffuse erythema on the extremities, a purple purpuric rash on the extensor face of both legs, and millimetric pustules on an erythematous base on the inner surface of the left arm. She stated that the reaction developed after taking 3 medications, including etodolac tablets, and gargling the throat with povidone-iodine. The patient was diagnosed with AGEP and her EuroSCAR AGEP Validation Score was calculated as 9 suggesting a definitive diagnosis of AGEP. All of the suspected drugs were discontinued. Methylprednisolone 16 mg/day, a local corticosteroid, and an oral antihistamine were started. Her symptoms resolved and laboratory abnormalities returned to normal within 2 weeks. Patch tests were performed 3 months after the reaction with the suspected drugs. The patch testing showed that only 10% etodolac at 48-, 72- and 96-hour readings were positive (++). The patient was diagnosed with AGEP due to etodolac. AGEP is often secondary reaction to drugs. The most frequent causative drugs are diltiazem, aminopenicillins, pristinamycin, terbinafine, sulphonamides, quinolones, and hydroxychloroquine. AGEP secondary to NSAIDs is very rare. Only one previous case of AGEP due to etodolac was reported in 2011. [ABSTRACT FROM AUTHOR]

Background: Intradermal testing (IDT) with iodinated contrast media (ICMs) is an established diagnostic tool in patients with ICM hypersensitivity. Currently, it is unclear which test concentration is the more useful one, up to pure or up to 1:10 diluted ICMs. Methods: We searched the literature database PubMed for eligible papers dealing with ICM allergy and their IDT results. We analyzed the data presented by the papers and compared the pooled groups tested with diluted and undiluted ICMs. Results: We identified 29 eligible original papers, and extracted data of 1137 patients that formed the study population. Although in the cohort tested with diluted ICMs the number of tested ICMs was greater, the percentage of positive tests was significantly less (9.0% vs. 24.7%; P < 0.0001; OR 0.30 [0.26–0.34]). The frequency of positive tested culprit ICMs was also lesser in the group tested with diluted ICMs (31.0% vs. 72.5%; P < 0.0001; OR 0.17 [0.12–0.23]). The number of drug provocation tests (DPTs) was greater in patients with diluted IDTs (374 vs. 89; P < 0.0001; OR 2.54 [1.93–3.36]). We detected an increased sensitivity in patients with undiluted tests (0.774 vs. 0.282) and a nearly identical specificity in both groups (1 vs. 0.983). Conclusions: For the first time, we show that IDT up to pure ICM concentrations is superior to using diluted ICMs only. Possibly, we can reduce the number of DPTs when performing IDTs with pure ICMs. In the undiluted group, there were no hints for skin irritations or unspecific test reactions. [ABSTRACT FROM AUTHOR]

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity reaction characterized by cutaneous rash, lymphadenopathy, fever, eosinophilia, leukocytosis, and life-threatening organ dysfunctions. We describe the case of a 26 year old patient admitted to the Emergency Department for DRESS syndrome after sulfasalazine treatment for rheumatoid arthritis in the right knee. Whole body computer tomography showed multiple neck, chest, and abdominal lymphadenopathy with splenomegaly, massive ascites and severe hepatic cytolysis. Serology results for Epstein-Barr Virus (EBV), influenza, measles, rubella, hepatitis A and B were negative. The histologic analysis of skin, lymph node and bone marrow biopsies could not indicate a classical Hodgkin's Disease or iatrogenic immunodeficiency/EBV-associated lymphoproliferative disorder (LPD), Hodgkin type. The relatively small caliber of the CD30 + immunoreactive blastoid cells in the lymph nodes suggested reactive immunoblasts rather than Hodgkin cells. The morphologic aspects of the lymph node biopsies with predominance of T-cells were compatible with the diagnosis of a sulfasalazine-induced DRESS syndrome as the patient had a high RegiSCAR score for DRESS. [DRESS Syndrome Foundation: Diagnosis and Treatment. (2023)] The patient's complex clinical course, marked by two hospital admissions, highlights the challenges in diagnosing and managing DRESS. This case underscores the need for individualized care, close patient monitoring, and further research to better understand DRESS's underlying mechanisms and optimal therapeutic strategies. [ABSTRACT FROM AUTHOR]

Drug hypersensitivity reactions (DHRs) are a type of adverse drug reaction that can occur with different classes of drugs and affect multiple organ systems and patient populations. DHRs can be classified as allergic or non-allergic based on the cellular mechanisms involved. Whereas nonallergic reactions rely mainly on the innate immune system, allergic reactions involve the generation of an adaptive immune response. Consequently, drug allergies are DHRs for which an immunological mechanism, with antibody and/or T cell, is demonstrated. Despite decades of research, methods to predict the potential for a new chemical entity to cause DHRs or to correctly attribute DHRs to a specific mechanism and a specific molecule are not well-established. This review will focus on allergic reactions induced by systemically administered low-molecular weight drugs with an emphasis on drug- and patient-specific factors that could influence the development of DHRs. Strategies for predicting and diagnosing DHRs, including potential tools based on the current state of the science, will also be discussed. [ABSTRACT FROM AUTHOR]

In Australia, neuromuscular blocking agents are the leading cause of perioperative anaphylaxis. Current investigation of suspected anaphylaxis includes tryptase levels, serum immunoglobulin E (IgE) levels, and skin testing, including intradermal testing and skin prick testing. The gold standard for the diagnosis of a hypersensitivity reaction is a challenge test, but this poses a risk to patient safety. An alternative test, known as the basophil activation test (BAT) is a form of cellular in vitro testing using flow cytometry to measure the degree of basophil degranulation within a sample of blood following exposure to an allergen. This acts as a surrogate marker for mast cell and basophil activation, thereby identifying IgE-mediated allergy. It is most commonly used to supplement equivocal findings from initial in vitro testing to assist in confirming the diagnosis of a hypersensitivity reaction and identify the causative agent. We present a case series in which five patients with suspected anaphylaxis underwent a BAT, demonstrating its role and limitations in allergy testing within Australia. [ABSTRACT FROM AUTHOR]

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Cutibacterium avidum is a well-known skin commensal, that sometimes can cause superficial or invasive infections, including infectious endocarditis. Cases of C. avidum-induced infectious endocarditis of native heart valves, prosthetic valves or other cardiac implantable devices are described, which is associated with the biological feature of the pathogen with a tendency to form biofilms. The article presents a clinical case of infectious endocarditis, caused by C. avidum, associated with implantation of pacemaker in 42-yearold patient with a history of multiple drug hypersensitivity reactions to antibacterial drugs. This individual feature interfered with effective antibacterial therapy of local infection of the intracardiac device, which led to the development of infectious endocarditis with vegetations, required surgery with tricuspid valve repair and pacemaker replacement.

Background: Screening and treating healthcare workers (HCWs) for latent tuberculosis infection (LTBI) are essential for tuberculosis (TB) infection control. Adverse drug reactions (ADRs) to anti-TB drugs present challenges to patient safety and treatment completion. Objective: This study investigated the association between human leukocyte antigen (HLA) alleles and the risk of ADRs, especially drug hypersensitivity (DHS) and hepatotoxicity, in HCWs with LTBI receiving isoniazid (INH) and rifampin (RIF) therapy. Methods: Korean HCWs with LTBI who received a 3 month INH and RIF regimen were included in this study. HLA genotyping was performed on HCWs who experienced ADRs during treatment, as well as the control group consisted of individuals who did not develop ADRs. Results: Of the 67 patients, 29 (43.2%) experienced ADRs during INH and RIF therapy. The HLA-A*11:01 allele was more frequent in patients with DHS without hepatotoxicity (DSH+/H−) compared to the control group (DHS−/H−) (4/9, 44.4% vs. 3/38, 7.9%; odd ratio [OR], 8.554; 95% confidence interval [CI], 1.415–59.869; p = 0.018). Conversely, HLA-DPB1*05:01 was associated with an increased risk of hepatotoxicity regardless of DHS (10/20, 50% vs. 5/38, 13.2%; OR, 5.323; 95% CI, 1.493–21.518; p = 0.011). In the DHS with hepatotoxicity group (DHS+/H+), HLA-DPB1*05:01 was present in a higher proportion (3/5, 60% vs. 5/38, 13.2%; OR, 8.912; 95% CI, 1.110–92.993; p = 0.037), whereas HLA-A*11:01 was not observed in this group. Conclusions: The HLA-A*11:01 allele was associated with an increased risk of DHS without hepatotoxicity, whereas the HLA-DPB1*05:01 allele was associated with an increased risk of hepatotoxicity. [ABSTRACT FROM AUTHOR]

Purpose: Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness. Methods: Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation. Results: We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019). Conclusion: These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness. [ABSTRACT FROM AUTHOR]

Introduction: Iron deficiency is the most common cause of anemia in both sexes, although it is more common in women. Intravenous (IV) iron replacement is preferred in patients who cannot tolerate oral treatment or when iron stores need to be replenished rapidly. In this study, we wanted to share the ferric carboxymaltose (FCM) desensitization protocol that we self-created and successfully applied. Methods: This retrospective cross-sectional study included patients with a history of hypersensitivity reactions (HSRs) to IV or oral iron replacement and patients who were planned to receive IV iron replacement but were referred to the allergy clinic because of have risk factors (atopic diseases, history of HSR to other drugs, high serum tryptase levels, etc.) for HSRs. Before desensitization, some of the patients underwent skin tests (skin prick test and intradermal test) with FCM, and the results were recorded. Skin tests were not performed in patients with a history of drug use (antihistamine, systemic steroid, omalizumab, etc.) that affected the results of skin tests. All patients underwent a one-bag 8-step desensitization protocol with 500 mg FCM and were observed for 2 h after desensitization. Results: A total of 15 patients (14 females and 1 male) with a mean age of 41.13 ± 11.18 years were included in the study. When the patients were evaluated in terms of the risk of allergic reactions according to their clinical history, 8 patients had a history of anaphylaxis with iron preparations (FCM, n = 4; ferric hydroxide sucrose, n = 2; iron [II] glycine sulfate, n = 1; and iron [III] hydroxide polymaltose, n = 1), and 7 patients had a history of HSR other than anaphylaxis with iron preparations (urticaria, n = 6 [FCM, n = 2; iron (II) glycine sulfate, n = 2; and iron (III) hydroxide polymaltose, n = 2] and urticaria + angioedema [ferric hydroxide sucrose, n = 1]). Desensitization was successfully completed in all patients. No HSR was observed during or after the procedure in any of the patients. Conclusion: IV iron replacement is a very effective method, especially in cases where iron stores need to be replenished more rapidly. In patients with a history of iron HSR or at risk of developing HSR, replacement can be safely performed without an allergic reaction with successful desensitization protocols. [ABSTRACT FROM AUTHOR]

Background: Asparaginase (ASNase) is a crucial part of acute leukemia treatment, but immune responses to the agent can reduce its effectiveness and increase the risk of relapse. Currently, no reliable and validated biomarker predicts ASNaseinduced hypersensitivity reactions during therapy. We aimed to identify predictive biomarkers and determine immune cells responsible for anaphylaxis using a murine model of ASNase hypersensitivity. Methods: Our preclinical study uses a murine model to investigate predictive biomarkers of ASNase anaphylaxis, including anti-ASNase antibody responses, immune complex (IC) levels, ASNase-specific binding to leukocytes or basophils, and basophil activation. Results: Our results indicate that mice immunized to ASNase exhibited dynamic IgM, IgG, and IgE antibody responses. The severity of ASNase-induced anaphylaxis was found to be correlated with levels of IgG and IgE, but not IgM. Basophils from immunized mice were able to recognize and activate in response to ASNase ex vivo, and the extent of recognition and activation also correlated with the severity of anaphylaxis observed. Using a multivariable model that included all biomarkers significantly associated with anaphylaxis, independent predictors of ASNase-induced hypersensitivity reactions were found to be ASNase IC levels and ASNase-specific binding to leukocytes or basophils. Consistent with our multivariable analysis, we found that basophil depletion significantly protected mice from ASNase-induced hypersensitivity reactions, supporting that basophils are essential and can be used as a predictive marker of ASNase-induced anaphylaxis. Conclusions: Our study demonstrates the need for using tools that can detect both IC- and IgE-mediated hypersensitivity reactions to mitigate the risk of ASNase-induced hypersensitivity reactions during treatment. [ABSTRACT FROM AUTHOR]

Background: Drug hypersensitivity is a major global public health issue with a significant increase in prevalence in populations. Here, we provide a deep insight into the frontier hotspot and future direction in the field of drug hypersensitivity. Methods: A knowledge map is portrayed based on publications related to drug hypersensitivity from Web of Science Core Collection using CiteSpace. Co‐occurrence relationships of countries, institutes, authors, journals, references, and keywords are constructed. According to the co‐occurrence relationships, hotspots and future trends are overviewed. Results: The United States ranked first in the world and China with the second highest publications was the only developing country. Torres, Mayorga, and Blanca were highly productive authors. Harvard University was the institution with the most research publications. Keywords co‐occurrence analysis suggested applications in emerging causes, potential mechanisms, and clinical diagnosis as the research hotspots and development frontiers. Conclusion: Research on drug hypersensitivity is in a rapid development stage and an emerging trend in reports of anaphylaxis to polyethylene glycols is identified. Developing algorithms for understanding the standardization process of culprit drugs, clinical manifestations, and diagnostic methods will be the focus of future direction. In addition, a better understanding of the mechanisms to culprit drugs with immunological precise phenotypic definitions and high‐throughput platforms is needed. [ABSTRACT FROM AUTHOR]

Abstract Notifications of invasive group A streptococcal (iGAS) infections have significantly increased in many European Countries compared to the previous season. In Italy, there has been an increase in streptococcal pharyngitis and scarlet fever cases since January 2023, which sparked concerns about a GAS epidemic in the pediatric population. This rise may be ascribed to the GAS infection season that began earlier than usual (off-season outbreak) and the increase in the spread of respiratory viruses and viral coinfections that raised the risk of iGAS disease. Moreover, this phenomenon was also facilitated by increased travel after reduced GAS circulation during the COVID-19 pandemic. The increase in cases of GAS disease has raised some critical issues regarding the potential reactions to administering amoxicillin, the first-line antibiotic therapy, many of which have been erroneously labeled as “allergy." For these reasons, the Italian Society of Pediatric Allergy and Immunology (SIAIP) intends to provide simple clinical indications to help pediatricians manage GAS pharyngitis, discerning the allergic from non-allergic drug hypersensitivity.

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.

Anaphylactic reaction during general anaesthesia represents a rare event in clinical practice with a possible fatal outcome. We present a case of a female patient with no prior history of allergic reactions to rocuronium. Shortly after rocuronium administration, she developed the following signs: tachycardia, low blood pressure and bronchospasm. Skin rash and peripheral signs were absent, probably due to previous premedication. Events like this could be potentially fatal if not recognized and treated in time. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well‐known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%–3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence‐based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in‐depth investigations in the topic. [ABSTRACT FROM AUTHOR]