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Background: Penicillin-associated exanthems in the setting of infectious mononucleosis caused by Epstein-Barr virus (EBV) are often viewed as a transient event, not a true allergy. Recent evidence challenges this and suggests that a notable subset of patients retain penicillin hypersensitivity. Objective: We investigated the occurrence and predictors of persistent adulthood hypersensitivity in those with penicillin-associated rash occurring in the setting of EBV infection. Methods: Retrospective analysis of data of patients referred for penicillin allergy testing to an Australian tertiary-care hospital captured from 2015 to 2023 was carried out. Results: Of 2066 patients, 23 (1%) had penicillin-associated rash during an historic EBV infection; 16 (70%) were female; and median (interquartile range) age was 18 (16-20) years at index reaction and 38 (33.5-57) years at allergy testing. Skin prick testing and delayed intradermal testing to a penicillin panel were performed, followed by oral provocation challenge in those testing negative. Persistent sensitization was shown in 6 (26%) of 23; 4 (67%) of 6 positive delayed intradermal testing; and 3 (50%) of 6 had positive oral challenge test. Notably, 5 (83%) of 6 had a severe maculopapular exanthem with facial swelling, including 2 (33%) of 6 with probable drug reaction with eosinophilia and systemic symptoms (aka DRESS) during the index reaction, compared to 0 of 17 in patients tolerating penicillin on reexposure. Conclusion: This study highlights the requirement of allergy testing in adult patients reporting a penicillin-associated severe maculopapular exanthem in the setting of EBV, even if it occurred during childhood or adolescence.

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When approaching a case of apparent drug allergy, the consulting clinician should consider a broad differential diagnosis. This article presents a series of cases that could be commonly referred to an allergist for assessment as "drug allergy," however, a real diagnosis exists that mandates a different diagnostic and treatment strategy, including a case of inducible laryngeal obstruction, multiple drug intolerance syndrome, viral rash, seizure due to metastatic malignancy, and hemophagocytic lymphohistiocytosis initially diagnosed as drug reaction and eosinophilia with systemic symptoms. The initial misdiagnoses of these patients delayed or interfered with their medical care, emphasizing the importance of accurate diagnoses for the benefit of our patients.

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Importance: Fewer than 5% of patients labeled with a penicillin allergy are truly allergic. The standard of care to remove the penicillin allergy label in adults is specialized testing involving prick and intradermal skin testing followed by an oral challenge with penicillin. Skin testing is resource intensive, limits practice to specialist-trained physicians, and restricts the global population who could undergo penicillin allergy delabeling. Objective: To determine whether a direct oral penicillin challenge is noninferior to the standard of care of penicillin skin testing followed by an oral challenge in patients with a low-risk penicillin allergy. Design, Setting, and Participants: This parallel, 2-arm, noninferiority, open-label, multicenter, international randomized clinical trial occurred in 6 specialized centers, 3 in North America (US and Canada) and 3 in Australia, from June 18, 2021, to December 2, 2022. Eligible adults had a PEN-FAST score lower than 3. PEN-FAST is a prospectively derived and internationally validated clinical decision rule that enables point-of-care risk assessment for adults reporting penicillin allergies. Interventions: Patients were randomly assigned to either direct oral challenge with penicillin (intervention arm) or a standard-of-care arm of penicillin skin testing followed by oral challenge with penicillin (control arm). Main Outcome and Measure: The primary outcome was a physician-verified positive immune-mediated oral penicillin challenge within 1 hour postintervention in the intention-to-treat population. Noninferiority was achieved if a 1-sided 95% CI of the risk difference (RD) did not exceed 5 percentage points (pp). Results: A total of 382 adults were randomized, with 377 patients (median [IQR] age, 51 [35-65] years; 247 [65.5%] female) included in the analysis: 187 in the intervention group and 190 in the control group. Most patients had a PEN-FAST score of 0 or 1. The primary outcome occurred in 1 patient (0.5%) in the intervention group and 1 patient (0.5%) in the control group, with an RD of 0.0084 pp (90% CI, -1.22 to 1.24 pp). The 1-sided 95% CI was below the noninferiority margin of 5 pp. In the 5 days following the oral penicillin challenge, 9 immune-mediated adverse events were recorded in the intervention group and 10 in the control group (RD, -0.45 pp; 95% CI, -4.87 to 3.96 pp). No serious adverse events occurred. Conclusions and Relevance: In this randomized clinical trial, direct oral penicillin challenge in patients with a low-risk penicillin allergy was noninferior compared with standard-of-care skin testing followed by oral challenge. In patients with a low-risk history, direct oral penicillin challenge is a safe procedure to facilitate the removal of a penicillin allergy label. Trial Registration: ClinicalTrials.gov Identifier: NCT04454229.

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This cohort study describes the adaptation of a widely used penicillin allergy clinical decision tool for evaluation of trimethoprim-sulfamethoxazole allergy.

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Inpatient direct oral challenge programs are increasingly deployed as part of antimicrobial stewardship initiatives to reduce the burden and impacts of penicillin allergy labels on antibiotic prescribing. Using data from a prospective, multicenter cohort inpatient penicillin allergy program, we identify the key targets for delabeling to aid health service implementation.

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Antibiotic allergy labels (AALs) are commonly reported, with well-defined prevalence in the general population; several studies have now focused efforts on immunocompromised hosts. Understanding the prevalence of reported allergy labels and methods of antibiotic allergy evaluation and delabeling strategies has the potential to improve prescribing practices and clinical outcomes in this high-antibiotic use group. In this review, we will discuss the current literature on the prevalence, impact, and evaluations of AALs in immunocompromised hosts with a focus on beta-lactam (penicillin) allergy and sulfa-antibiotic (antimicrobial sulfurs) allergy labels.

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Biologic medications are an expanding field of therapeutics for various medical conditions including cancer and inflammatory diseases. Due to their targeted approach to therapy, biologics can be less toxic than traditional systemic medications. However, as use becomes more widespread, adverse effects from biologic administration have also become apparent. Immune-related adverse events are a common mechanism by which biologics can cause on-target immune-related toxicities and both immediate and delayed-type hypersensitivity reactions. Immediate hypersensitivity reactions can be mediated by cytokine release or antibody mediated reactions, while delayed-type hypersensitivity is most often caused by serum sickness-like reactions. Additionally, biologics used for treatment of cancer using checkpoint blockade and rheumatologic disease using cytokine blockade can result in autoimmunity. Finally, when inflammatory cytokines are targeted for treatment of autoimmune or autoinflammatory disease, the host immune defense can be compromised predisposing to secondary immunodeficiency. This review will discuss the mechanisms of these reactions and discuss examples of biologics implicated in each of these adverse events.

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OBJECTIVE: To estimate the feasibility, acceptability, and safety of outpatient penicillin allergy testing among pregnant women. METHODS: We conducted a prospective cohort study at a large academic hospital from March 2019 to March 2020. We recruited pregnant women with a self-reported penicillin allergy who underwent allergy testing between 14 0/7 and 36 6/7 weeks of gestation. RESULTS: Of 127 eligible women pregnant women, 74 (58%, 95% CI 4-67%) accepted allergy testing. Fifty completed or intended to complete allergy testing, yielding a feasibility rate of 68% (95% CI 56-78%). Among the 46 women actually tested (who ranged in age from 18 to 42), 93% (95% CI 68-100%) had a negative test result. A systemic reaction (symptoms consistent with anaphylaxis) occurred in only 2 women (4%, 95% CI 0.5-15%) despite 20 (43%) reporting a severe allergy. No woman suffered an adverse event as a result of allergy testing. In multivariate analysis adjusting for age and parity, women with public insurance had decreased odds of undergoing penicillin allergy testing (adjusted odds ratio 0.24, 95% CI 0.08-0.69). CONCLUSION: Outpatient penicillin allergy testing is acceptable and feasible in pregnancy.

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This article reviews research advances for sublingual and patch immunotherapy for food allergy with a focus on peanut allergy. Published studies on sublingual immunotherapy (SLIT) and epicutaneous immunotherapy (EPIT) were summarized in this review. Sublingual and epicutaneous methods have emerged as alternatives to oral immunotherapy. SLIT studies have shown modest desensitization with a robust safety profile. EPIT studies have high adherence rates, an excellent safety profile, and potential for desensitization in children. Advances in food immunotherapy with SLIT and EPIT studies have shown promise as viable alternatives to oral immunotherapy for treatment of patients with peanut food allergy.

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Objectives To estimate the prevalence of and identify modifiable risk factors for alternative antibiotics for group B Streptococcus (GBS) prophylaxis in penicillin-allergic women. Methods Retrospective cohort study of pregnant women within a health care network from January 1, 2014, to December 31, 2017. Included women were GBS colonized, delivered at ≥ 37 weeks' gestation, and reported penicillin/cephalosporin allergy. The primary outcome was the use of alternate antibiotics GBS prophylaxis, defined per Centers for Disease Control and Prevention guidelines as antibiotics other than penicillin, ampicillin, or cefazolin. Results We identified 190 GBS-colonized pregnant women self-reporting a penicillin/cephalosporin allergy; 5% reported anaphylaxis, 44% high-risk symptoms (isolated hives, shortness of breath, swelling, or vomiting), and 51% low-risk symptoms (isolated rash, itching, or nausea). Two-thirds (63%) had alternative antibiotic prophylaxis. In adjusted analyses, nonwhite race (adjusted odds ratio [aOR]: 2.42; 95% confidence interval [CI]: 1.19-4.94) and high-risk allergic reaction (aOR: 2.42; 95% CI: 1.30-4.49) were associated with higher odds of alternative antibiotics prophylaxis compared with low-risk allergic reaction. Low-risk allergic reaction group was less likely to receive alternative antibiotic prophylaxis (aOR: 0.36; 95 CI%: 0.19-0.66). Conclusion Alternative antibiotic use for GBS prophylaxis is frequent with penicillin/cephalosporin allergies. Efforts to confirm allergy and perform penicillin hypersensitivity testing may increase compliance with guidelines for antibiotic administration.