Penicillin allergy is frequently reported yet rarely confirmed in pregnant women, similar to the general population. Historically, there has been hesitation to perform penicillin allergy testing in pregnant patients due to perceived risk to the patient and fetus in the event of an allergic reaction. Given the multiple clinical indications for penicillin in pregnancy and delivery, there are also risks of using non-first-line antibiotics; thus clarity is needed regarding the safety of undergoing penicillin allergy testing during pregnancy. A workgroup subcommittee of members from the American Academy of Allergy, Asthma & Immunology committees on Women's Health in Allergy/Immunology and Adverse Reactions to Drugs, Biologics, and Vaccines was convened, and a survey of current allergist practices as well as a scoping review of the literature was conducted. Although survey respondents reported mixed comfort with testing, evidence from numerous recent studies representing hundreds of pregnant patients demonstrates that penicillin allergy testing can be safely performed via an oral challenge with or without preceding skin testing. To implement this testing in clinical practice, allergists and immunologists can learn from the clinical experience of numerous institutions that have reported a successful approach to offering definitive allergy evaluation in this population.

Shared decision-making (SDM) is a cornerstone of patient-centered care that integrates clinical expertise with patient values to guide healthcare decisions. In drug allergy, SDM is particularly critical due to the inherent need of balancing risks of intervention (eg, skin testing, rechallenge, or desensitization) and risks of avoidance (eg, second-line therapies and for patients with antibiotic allergy, increased costs, suboptimal treatment, and antimicrobial resistance). Patients carrying drug allergy labels, including both survivors of severe reactions and those with unverified drug allergies, have associated reductions in quality of life and overall psychological well-being, often exhibiting heightened anxiety, depression, and distress when taking medications. Recent studies demonstrate that drug allergy evaluation leads to meaningful improvements in quality of life for these patients. However, patient reluctance and concerns remain major barriers to drug allergy evaluation and appropriate treatment. SDM addresses these barriers by facilitating discussions that incorporate patient preferences to foster trust and engagement. Integrating SDM throughout the drug allergy care continuum, from initial labeling to diagnostic evaluation and management, can assist with patient acceptance of recommendations, improved adherence, and ultimately optimized clinical outcomes and quality of life.

Penicillin allergy labels are a major barrier to optimal antimicrobial stewardship, yet most reported reactions are inaccurate and can be safely removed after evaluation. This Clinical Management Review article summarizes lessons from population-level delabeling initiatives, highlighting the value of incorporating nonallergist perspectives and practical implementation tools. Effective strategies extend beyond specialist settings and rely on multidisciplinary engagement-including primary care, pharmacy, and nursing-to scale interventions. A practical toolkit offering standardized risk-stratification algorithms, oral challenge protocols, and communication templates supports safe and efficient delabeling across diverse clinical environments. Psychosocial and equity considerations are critical to delabeling success. Fear, misinformation, and cultural beliefs often shape patients' willingness to undergo evaluation, while systemic barriers-such as limited specialist access, language differences, and resource constraints-contribute to disparities. Programs that embed patient-centered education, shared decision making, and flexible delivery models show improved uptake and long-term sustainability. Equity-focused approaches, including outreach to underserved communities and integration into routine care pathways, are essential to achieving broad impact. By combining evidence-based protocols with practical tools and inclusive stakeholder engagement, health systems can overcome logistical and psychosocial challenges to meaningfully reduce the number of inappropriate penicillin allergy labels. These lessons underscore the need for adaptable, equity-driven strategies to optimize antimicrobial use and improve patient outcomes.

The authors declare no conflicts of interest. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Unverified penicillin allergy labels are common and can result in preventable maternal and neonatal adverse outcomes. The American College of Obstetricians and Gynecologists recommends evaluation of penicillin allergies in pregnancy to aid in preventing neonatal morbidity and mortality from Group B streptococcal disease. Historically, the standard-of-care procedure has been penicillin skin testing followed by penicillin challenge. However, direct oral challenge (DOC) is becoming increasingly accepted as the standard of care for patients with low-risk reaction histories. This narrative review presents a pro-con discussion regarding the use of DOCs during pregnancy. We highlight the large body of data supporting the use of penicillin skin testing followed by penicillin challenge in both pregnant and nonpregnant patients, noting that skin testing has captured sensitization to penicillin, potentially averting severe allergic reactions that could have occurred on penicillin administration. On the other side of the debate, we underscore evidence from observational studies, randomized clinical trials, and meta-analyses in support of DOCs, especially in patients who have been appropriately risk-stratified, including studies focused on pregnant patients. We emphasize how DOCs may aid in addressing disparities in delabeling. Finally, we emphasize the importance of shared decision making and other evidence-based approaches to enhance first-line antibiotic use during pregnancy.

BACKGROUND:Using the reaction history in logistic regression and machine learning (ML) models to predict penicillin allergy has been reported based on non-US data. OBJECTIVE:We developed ML positive penicillin allergy testing prediction models from multisite US data. METHODS:Retrospective data from 4 US-based hospitals were grouped into 4 datasets: enriched training (1:3 case-control matched cohort), enriched testing, nonenriched internal testing, and nonenriched external testing. ML algorithms were used for model development. We determined area under the curve (AUC) and applied the Shapley Additive exPlanations (SHAP) framework to interpret risk drivers. RESULTS:Of 4777 patients (mean age 60 [standard deviation: 17] years; 68% women, 91% White, and 86% non-Hispanic) evaluated for penicillin allergy labels, 513 (11%) had positive penicillin allergy testing. Model input variables were frequently missing: immediate or delayed onset (71%), signs or symptoms (13%), and treatment (31%). The gradient-boosted model was the strongest model with an AUC of 0.67 (95% confidence interval [CI]: 0.57-0.77), which improved to 0.87 (95% CI: 0.73-1) when only cases with complete data were used. Top SHAP drivers for positive testing were reactions within the last year and reactions requiring medical attention; female sex and reaction of hives/urticaria were also positive drivers. CONCLUSIONS:An ML prediction model for positive penicillin allergy skin testing using US-based retrospective data did not achieve performance strong enough for acceptance and adoption. The optimal ML prediction model for positive penicillin allergy testing was driven by time since reaction, seek medical attention, female sex, and hives/urticaria.

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.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected disadvantaged populations. Many of the factors related to the disproportionate impact on underserved communities are related to social determinants of health, defined by the World Health Organization as the nonmedical factors that influence health outcomes. They include the wider set of forces and systems shaping the conditions of daily life. This work explores the interrelationships between social determinants of health and access to care, health care professional and supply shortages, social and environmental factors, health behaviors, vaccine uptake, and treatment options on COVID-19 health outcomes. Increased awareness of inequities, learning from failures, and leveraging new opportunities to partner with key stakeholders in underserved communities create empowerment and preparedness to face new challenges.

Across all settings, women self-report more drug allergies than do men. Although there is epidemiologic evidence of increased drug allergy labeling in postpubertal females, the evidence base for female sex as a risk factor for true immune-mediated drug hypersensitivity reactions (DHRs), particularly in fatal druginduced anaphylaxis, is low. A focus on the known immunologic mechanisms described in immediate and delayed DHR, layered on known hormonal and genetic sex differences that drive other immune-mediated diseases, could be the key to understanding biological sex variations in DHR. Particular conditions that highlight the impact of drug allergy in women include (1) pregnancy, in which a drug allergy label is associated with increased maternal and fetal complications; (2) multiple drug intolerance syndrome, associated with anxiety and depression; and (3) female-predominant autoimmune medical conditions in the context of mislabeling of the drug allergy or increased underlying risk. In this review, we describe the importance of drug allergy in the female population, mainly focusing on the epidemiology and risk, the mechanisms, and the associated conditions and psychosocial factors. By performing a detailed analysis of the current literature, we provide focused conclusions

PURPOSE OF REVIEW:We review the literature and discuss the logistics of testing pregnant patients for penicillin allergy.RECENT FINDINGS:As in the general population, pregnant patients commonly report a penicillin allergy, but most patients are able to tolerate penicillin. Avoidance of beta-lactams in pregnancy is associated with increased morbidity: longer hospitalizations, more frequent infections, and more complications. Penicillin allergy testing is safe in pregnant patients, and obstetricians are eager for allergists to offer this procedure to their patients. As allergists, we can improve our patients' health outcomes by offering penicillin allergy testing in our practices. The protocols for testing both with and without skin testing in pregnant patients have been studied, and future studies will continue to clarify the safety and efficacy of penicillin allergy delabeling in pregnant patients.

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.

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.

The COVID-19 vaccines have proved essential in our defense against the COVID-19 pandemic. However, concerns regarding allergic reactions to the vaccines persist to this day. Herein, we review the data regarding the frequency of allergic reactions to the COVID-19 vaccines, the epidemiology, and the management of patients reporting vaccine allergic reactions. Although initial reports emphasized a high risk of anaphylaxis to the COVID-19 vaccines, more recent data demonstrate similar rates of anaphylaxis to the COVID-19 vaccines as to other vaccines. Alternative explanations for increased rates of apparent allergic reactions are discussed, including the role for stress-related and nocebo responses. COVID-19 vaccines and mRNA vaccine technology are overwhelmingly safe and well-tolerated by most patients. Careful history and case review will enable the discerning physician to safely vaccinate most patients. Rare patients with objective signs and symptoms of anaphylaxis may be candidates for alternatives to vaccination including monoclonal antibodies.

BACKGROUND: Although immediate potentially allergic reactions have been reported after dose 1 of mRNA coronavirus disease 2019 (COVID-19) vaccines, comprehensively defined subtypes have not been clearly distinguished.OBJECTIVE: To define distinct clinical phenotypes of immediate reactions after dose 1 of mRNA COVID-19 vaccination, and to assess the relation of clinical phenotype to mRNA COVID-19 vaccine second dose tolerance.METHODS: This retrospective study included patients with 1 or more potentially allergic symptoms or signs within 4 hours of receiving dose 1 of an mRNA COVID-19 vaccine and assessed by allergy/immunology specialists from 5 U.S. academic medical centers (January -June 2021). We used latent class analysis- an unbiased, machine-learning modeling method-to define novel clinical phenotypes. We assessed demographic, clinical, and reaction characteristics associated with phenotype membership. Using log-binomial regression, we assessed the relation between phenotype membership and second dose tolerance, defined as either no symptoms or mild, self-limited symptoms resolving with antihistamines alone. A sensitivity analysis considered second dose tolerance as objective signs only.RESULTS: We identified 265 patients with dose-1 immediate reactions with 3 phenotype clusters: (1) Limited or Predomi-nantly Cutaneous, (2) Sensory, and (3) Systemic. A total of 223 patients (84%) received a second dose and 200 (90%) tolerated their second dose. Sensory cluster (all patients had the symptom of numbness or tingling) was associated with a higher likelihood of second dose intolerance, but this finding did not persist when accounting for objective signs.CONCLUSIONS: Three novel clinical phenotypes of immediate-onset reactions after dose 1 of mRNA COVID-19 vaccines were identified using latent class analysis: (1) Limited or Predominantly Cutaneous, (2) Sensory, and (3) Systemic. Whereas these clinical phenotypes may indicate differential mechanistic etiologies or associations with subsequent dose tolerance, most individuals proceeding to their second dose tolerated it. (c) 2022 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2023;11:458-65)

Importance Vaccination against SARS-CoV-2 is a highly effective strategy to prevent infection and severe COVID-19 outcomes. The best strategy for a second dose of vaccine among persons who had an immediate allergic reaction to their first SARS CoV-2 vaccination is unclear. Objective To assess the risk of severe immediate allergic reactions (eg, anaphylaxis) to a second dose of SARS-CoV-2 mRNA vaccine among persons with immediate allergic reactions to their first vaccine dose. Data Sources MEDLINE, Embase, Web of Science, and the World Health Organization Global Coronavirus database were searched from inception through October 4, 2021. Study Selection Included studies addressed immediate allergic reactions of any severity to a second SARS-CoV-2 vaccine dose in persons with a known or suspected immediate allergic reaction (<4 hours after vaccination) after their first SARS-CoV-2 vaccine dose. Studies describing a second vaccine dose among persons reporting delayed reactions (>4 hours after vaccination) were excluded. Data Extraction and Synthesis Paired reviewers independently selected studies, extracted data, and assessed risk of bias. Random-effects models were used for meta-analysis. The GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach evaluated certainty of the evidence. Main Outcomes and Measures Risk of severe immediate allergic reaction and repeated severe immediate allergic reactions with a second vaccine dose. Reaction severity was defined by the reporting investigator, using Brighton Collaboration Criteria, Ring and Messmer criteria, World Allergy Organization criteria, or National Institute of Allergy and Infectious Diseases criteria. Results Among 22 studies of SARS-CoV-2 mRNA vaccines, 1366 individuals (87.8% women; mean age, 46.1 years) had immediate allergic reactions to their first vaccination. Analysis using the pooled random-effects model found that 6 patients developed severe immediate allergic reactions after their second vaccination (absolute risk, 0.16% [95% CI, 0.01%-2.94%]), 232 developed mild symptoms (13.65% [95% CI, 7.76%-22.9%]), and, conversely, 1360 tolerated the dose (99.84% [95% CI, 97.09%-99.99%]). Among 78 persons with severe immediate allergic reactions to their first SARS-CoV-2 mRNA vaccination, 4 people (4.94% [95% CI, 0.93%-22.28%]) had a second severe immediate reaction, and 15 had nonsevere symptoms (9.54% [95% CI, 2.18%-33.34%]). There were no deaths. Graded vaccine dosing, skin testing, and premedication as risk-stratification strategies did not alter the findings. Certainty of evidence was moderate for those with any allergic reaction to the first dose and low for those with severe allergic reactions to the first dose. Conclusions and Relevance In this systematic review and meta-analysis of case studies and case reports, the risk of immediate allergic reactions and severe immediate reactions or anaphylaxis associated with a second dose of an SARS-CoV-2 mRNA vaccine was low among persons who experienced an immediate allergic reaction to their first dose. These findings suggest that revaccination of individuals with an immediate allergic reaction to a first SARS-CoV-2 mRNA vaccine dose in a supervised setting equipped to manage severe allergic reactions can be safe.

A healthy 27-year-old woman received a COVID-19 mRNA booster vaccine (Moderna) on December 7, 2021.She had not experienced adverse effects after the first 2 vaccine doses on January 17 and February 5, 2021.Twelve days after the booster vaccination, she developed pruritic wheals on her face and bilateral, transient eyelid swelling.Over the next week, a pruritic rash spread over her neck, chest, trunk, and arms; each lesion faded without scarring within 24 hours.She did not experience lip, tongue, or neck swelling; shortness of breath; wheezing; chest pain; or palpitations.Application of pressure to her forearm in a circular motion using a pen cap elicited wheal and flare lesions (Figure, left panel).On physical examination, performed 17 days after the onset of rash, her vital signs were normal.She had no tongue, lip, or throat swelling, and her lungs were clear to auscultation bilaterally.Wheal and flare lesions developed on her upper eyelids during the examination and resolved after approximately 30 minutes (Figure, right panel).Light pressure applied to her skin with a tongue depressor elicited wheal and flare lesions within 3 to 5 minutes.The patient had no history of atopy, urticaria, angioedema, or food or drug allergy and no recent infections.She took no prescription medications and reported no recent use of over-the-counter medications, including nonsteroidal anti-inflammatory drugs.She had no recent travel, exposure to animals, or use of new personal care products. Diagnosis