A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.

BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. OBJECTIVE: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. METHODS: A systematic review of the literature was performed, and an expert Delphi Panel was assembled. RESULTS: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. CONCLUSION: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.

Evaluation of patients labeled with a penicillin allergy to promote antimicrobial stewardship in dental practice.

BACKGROUND: Approximately 10% of the US population self-reports a penicillin allergy history or are labeled as penicillin allergic. However, from 90% through 99% of these patients are not allergic on formal evaluation. CASE DESCRIPTION: Patients labeled as penicillin allergic receive broader-spectrum and sometimes less-effective antibiotics, thereby contributing to increased treatment failures, antibiotic resistance, and adverse drug reactions. Self-reported penicillin allergy can be eliminated or classified as low-, medium-, or high-risk after a careful review of patient history. This allows these patients to be delabeled; that is, having any reference to their penicillin allergy history or of having an allergy to penicillin eliminated from their health records. PRACTICAL IMPLICATIONS: Oral health care professionals are ideally placed to partner in both antibiotic stewardship interventions by means of recognizing pervasive mislabeling and aiding in the process of delabeling.

How to Define and Manage Low-Risk Drug Allergy Labels.

Risk stratification in drug allergy implies that specific risk categories (eg, low, moderate, and high) classify historical drug hypersensitivity reactions. These risk categories can be based on reaction phenotypic characteristics, the timing of the reaction and evaluation, the required reaction management, and individual characteristics. Although a multitude of frameworks have been described in the literature, particularly for penicillin allergy labels, there has yet to be a global consensus, and approaches continue to vary between allergy centers. Immune-mediated drug allergies can sometimes be confirmed using skin testing, but a negative drug challenge is required to demonstrate tolerance and remove the allergy from the electronic health record ("delabel" the allergy). Even for quintessential IgE-mediated drug allergy, penicillin allergy, recent data reveal that a direct oral challenge, without prior skin testing, is an appropriate diagnostic strategy in those who are considered low-risk. Drug allergy pathogenesis and clinical manifestations may vary depending on the culprit drug, and as such, the optimal approach should be based on risk stratification that considers individual patient and reaction characteristics, the likely hypersensitivity reaction phenotype, the drug class, and the patient's clinical needs. This article will describe low-risk drug allergy labels, focusing on ß-lactam and sulfonamide antibiotics, nonsteroidal anti-inflammatory drugs, iodinated contrast media, and common chemotherapeutics. This review will also address practical management approaches using currently available risk stratification and clinical decision tools.

Improving Clinical Practice Through Patient Registries in Allergy and Immunology.

Patient registries are a mechanism for collecting data on allergic and immunologic diseases that provide important information on epidemiology and outcomes that can ultimately improve patient care. Key criteria for establishing effective registries include the use of a clearly defined purpose, identifying the target population and ensuring consistent data collection. Registries in allergic diseases include those for diseases such as inborn errors of immunity (IEI), food allergy, asthma and anaphylaxis, pharmacological interventions in vulnerable populations, and adverse effects of pharmacologic interventions including hypersensitivity reactions to drugs and vaccines. Important insights gained from patient registries in our field include contributions in phenotype and outcomes in IEI, the risk for adverse reactions in food-allergic patients in multiple settings, the benefits and risk of biologic medications for asthma during pregnancy, vaccine safety, and the categorization and genetic determination of risk for severe cutaneous adverse reactions to medications. Impediments to the development of clinically meaningful patient registries include the lack of funding resources for registry establishment and the quality, quantity, and consistency of available data. Despite these drawbacks, high-quality and successful registries are invaluable in informing clinical practice and improving outcomes in patients with allergic and immunological diseases.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs), which include Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also known as drug-induced hypersensitivity syndrome), acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption, are life-threatening conditions. The pathogenesis of SCARs involves T cell receptors recognizing drug antigens presented by human leukocyte antigens, triggering the activation of distinct T cell subsets. These cells interact with keratinocytes and various immune cells, orchestrating cutaneous lesions and systemic manifestations. Genetic predisposition, impaired drug metabolism, viral reactivation or infections, and heterologous immunity influence SCAR development and clinical presentation. Specific genetic associations with distinct SCAR phenotypes have been identified, leading to the implementation of genetic screening before prescription in various countries to prevent SCARs. Whilst systemic corticosteroids and conventional immunomodulators have been the primary therapeutic agents, evolving strategies, including biologics and small molecules targeting tumour necrosis factor, different cytokines, or Janus kinase signalling pathways, signify a shift towards a precision management paradigm that considers individual clinical presentations.

Predicting Penicillin Allergy: A United States Multicenter Retrospective Study.

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.

The impact of COVID-19 vaccine reactions on secondary vaccine hesitancy.

BACKGROUND: Primary and booster vaccinations are critical for mitigating COVID-19 transmission, morbidity, and mortality. Future booster vaccine campaigns rely on an increased understanding of vaccine hesitancy. OBJECTIVE: To evaluate self-reported allergic and skin vaccine reactions as factors potentially associated with vaccine hesitancy in a nationwide vaccine allergy registry. METHODS: Responses to survey questions concerning COVID-19 vaccine perceptions, coded from free text by 2 independent reviewers. Multivariable logistic regression models were used to determine the association between changed negative perception and respondent demographics, vaccination history, and reaction characteristics. RESULTS: A total of 993 individuals (median of 46 years [IQR, 36-59], 88% female, 82% White) self-reported reactions to COVID-19 vaccination. Reactions included the following: delayed large local skin reaction (40%), hives/urticaria (32%), immediate large local skin reaction (3%), swelling (3%), anaphylaxis (2%), and other or unspecified (20%). Most respondents were initially unconcerned about the safety of COVID-19 vaccines (56%). After reactions, 401 of 993 (40%) report negative change in perception of vaccination, with more than half of these respondents (n = 211, 53%) citing their reasoning as a negative experience with adverse effects. Of 102 individuals asked about future vaccination, 79 (77%) indicated that they were unlikely or very unlikely to receive future COVID-19 vaccinations. Increased negative perception after reaction was associated with younger age, later COVID-19 vaccination dose number, and reaction type. CONCLUSION: Our findings reveal that an individual's experience with allergic or cutaneous adverse effects after COVID-19 vaccination affects attitudes and decision-making regarding future vaccination, even in initially non-hesitant individuals. Further investigation of secondary vaccine hesitancy is necessary for adapting public health messaging to this important population.

Examining cefazolin utilization and perioperative anaphylaxis in patients with and without a penicillin allergy label: A cross-sectional study.

STUDY OBJECTIVE: To compare the occurrence of cefazolin perioperative anaphylaxis (POA) in patients with and without a penicillin allergy label (PAL) to determine whether the prevalence of cefazolin POA differs based on the presence of a PAL. DESIGN: Cross-sectional study. SETTING: A large U.S. healthcare system in the Baltimore-D.C. region, July 2017 to July 2020. PATIENTS: 112,817 surgical encounters across inpatient and outpatient settings in various specialties, involving 90,089 patients. Of these, 4876 (4.3%) encounters had a PAL. INTERVENTIONS: Perioperative cefazolin administration within 4 h before surgery to 4 h after the procedure began. MEASUREMENTS: The primary outcome was cefazolin POA in patients with and without PALs. Potential POA cases were identified based on tryptase orders or diphenhydramine administrations within the initial cefazolin administration to 6 h postoperatively. Verification included two validation steps. The first checked for hypersensitivity reaction (HSR) documentation, and the second, led by Allergy specialists, identified POA and the probable culprit. The secondary outcome looked at cefazolin use trends in patients with a PAL, stratified by setting and specialty. MAIN RESULTS: Of 112,817 encounters, 1421 (1.3%) had possible cefazolin HSRs. Of these, 22 (1.5%) had POA, resulting in a 0.02% prevalence. Of these, 13 (59.1%) were linked to cefazolin and 9 (40.9%) attributed to other drugs. Only one cefazolin POA case had a PAL, indicating no significant difference in cefazolin POA prevalence between patients with and without PALs (p = 0.437). Perioperative cefazolin use in patients with PALs steadily increased from 2.6% to 6.0% between 2017 and 2020, specifically in academic settings. CONCLUSIONS: The prevalence of cefazolin POA does not exhibit significant differences between patients with and without PALs, and notably, the incidence remains remarkably low. Based on these findings, it is advisable to view cefazolin as an acceptable choice for prophylaxis in patients carrying a PAL.

Low frequency of allergy referral for penicillin allergy evaluation in an urban Boston primary care setting.

Background: A key strategy to combat the public health crisis of antimicrobial resistance is to use appropriate antibiotics, which is difficult in patients with a penicillin allergy label. Objective: Our aim was to investigate racial and ethnic differences related to penicillin allergy labeling and referral to allergy/immunology in primary care. Methods: This was a retrospective study of Tufts Medical Center's Boston-based primary care patients in 2019. Univariable and multivariable logistic regression models were used to examine demographic associations with (1) penicillin allergy label and (2) allergist referral. Results: Of 21,918 primary care patients, 2,391 (11%) had a penicillin allergy label; of these, 249 (10%) had an allergist referral. In multivariable logistic regression models, older age (adjusted odds ratio [aOR] = 1.06 [95% CI = 1.04-1.09]) and female sex (aOR = 1.58 [95% CI = 1.44-1.74]) were associated with higher odds of penicillin allergy label carriage. Black race (aOR = 0.77 [95% CI = 0.69-0.87]) and Asian race (aOR = 0.47 [95% CI = 0.41-0.53]) were associated with lower odds of penicillin allergy label carriage. In multivariable regression, allergist referral was associated with female sex (aOR = 1.52 [95% CI = 1.10-2.10]) and Black race (aOR = 1.74 [95% CI = 1.25-2.45]). Of 93 patients (37%) who completed their allergy visit, 26 (28%) had received penicillin allergy evaluation or were scheduled to receive a penicillin allergy evaluation at a future visit. Conclusions: There were racial differences in penicillin allergy labeling and referral. Allergy referral for penicillin allergy assessment was rare. Larger studies are needed to assess penicillin allergy labeling and delabeling with an equity focus on optimizing patient health outcomes.

Fatal ampicillin-sulbactam anaphylaxis in a 34-year-old male.

A 34-year-old man receiving his first dose of ampicillin-sulbactam for osteomyelitis in a hospital setting experienced fatal drug-induced anaphylaxis.

United States Drug Allergy Registry (USDAR) grading scale for immediate drug reactions.

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.

Drug allergy in older adults: A study from the United States Drug Allergy Registry.

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.

An Update in COVID-19 Vaccine Reactions in 2023: Progress and Understanding.

It has been 3 years since the coronavirus disease 2019 (COVID-19) pandemic was initially declared, and 2 years have passed since the first COVID-19 vaccines were introduced. Since then, 13.2 billion COVID-19 vaccine doses have been administered worldwide, largely with multiple doses of messenger RNA vaccines. Although mild local and systemic adverse effects after COVID-19 vaccination are common, serious adverse effects following immunization are rare, particularly when compared with the large number of vaccine doses administered. Immediate and delayed reactions are relatively common and present similarly to allergic and hypersensitivity reactions. Despite this, reactions generally do not commonly recur, cause sequelae, or contraindicate revaccination. In this Clinical Management Review, we provide an updated perspective of COVID-19 vaccine reactions, their spectrum and epidemiology, and recommended approaches to evaluation and management.