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.

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.

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.

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.

Women in Allergy and Immunology: The Future Is Female, Let Us Soar!

Despite increases in the number of female physicians in the past 50 years, women remain underrepresented in key areas of medicine, such as practice owners and partners, professional society leaders, principal investigators, full professors, chairs, and deans. Women are paid less, oftentimes for more work. Allergy and Immunology (AI), as a specialty, lacks substantial workforce research, but trends across specialties are consistent. We review what is currently known about women in AI and consider barriers to practice, advancement, and contribution. Through a new inquiry, we find that the challenges women in AI encounter can be summarized through 6 themes: work-life balance, professional advancement, salary equity, mentorship and sponsorship, bias, and sexual harassment and misconduct. Together, we must address these challenges head-on and provide an equitable environment for women in AI to thrive, especially those affected by intersectionality. To do so, we suggest targeted, tangible actions to promote opportunities, offer institutional support, and advance reporting and culture change outlets across AI settings.

Impact of an Inpatient Allergy Guideline on ß-Lactam and Alternative Antibiotic Use.

BACKGROUND: A guideline identifying when inpatients with penicillin or cephalosporin antibiotic allergy labels (PCAAL) can receive ß-lactam antibiotics increased ß-lactam receipt at a large northeastern US health care system. OBJECTIVE: To report outcomes of implementing a similar guideline and electronic order set (OS) at an independent academic health care system. METHODS: Penicillin/cephalosporin receipt (percentage of inpatients receiving full doses) and alternative antibiotic use (days of therapy per 1000 patient-days [DOT/1000PD]) were compared over 3 periods before (February 1, 2017, to January 31, 2018) and after guideline implementation (February 1, 2018, to January 31, 2019), and after OS implementation (February 1, 2019, to January 31, 2020) among inpatients with PCAAL admitted on medical services with access to guideline/OS and education (Medical-PCAAL, n = 8721), surgical services with access to guideline/OS without education (Surgical-PCAAL, n = 5069), and obstetrics/gynecology services without interventions (Ob/Gyn-PCAAL, n = 798) and inpatients without PCAAL admitted on the same services (Medical-No-PCAAL, n = 50,840; Surgical-No-PCAAL, n = 29,845; Ob/Gyn-No-PCAAL, n = 6109). χ2 tests were used to compare categorical variables, and analysis of variance was used to compare continuous and interrupted time series analyses (ITSA) to investigate the guideline/OS implementation effect on penicillin/cephalosporin receipt. RESULTS: In the Medical-PCAAL group, penicillin/cephalosporin receipt increased (58%-68%, P < .001), specifically for cefazolin (8%-11%, P = .02) and third- to fifth-generation cephalosporins (43%-48%, P = .04), and aztreonam use decreased (12 DOT/1000PD, P = .03). In the Medical-No-PCAAL group, penicillin/cephalosporin receipt increased (88%-90%, P = .004), specifically for penicillin (40%-44%, P < .001), without changes in aztreonam use. Significant changes were not observed in these outcomes on surgical or obstetrics/gynecology services. Per ITSA, guideline/OS implementation was associated with increased penicillin/cephalosporin receipt in the Medical-PCAAL group only. CONCLUSION: Guideline and OS implementation was associated with improved antibiotic stewardship on inpatient services that also received allergy education.

A Novel Informatics Tool to Detect Periprocedural Antibiotic Allergy Adverse Events for Near Real-time Surveillance to Support Audit and Feedback.

Importance: Standardized processes for identifying when allergic-type reactions occur and linking reactions to drug exposures are limited. Objective: To develop an informatics tool to improve detection of antibiotic allergic-type events. Design, Setting, and Participants: This retrospective cohort study was conducted from October 1, 2015, to September 30, 2019, with data analyzed between July 1, 2021, and January 31, 2022. The study was conducted across Veteran Affairs hospitals among patients who underwent cardiovascular implantable electronic device (CIED) procedures and received periprocedural antibiotic prophylaxis. The cohort was split into training and test cohorts, and cases were manually reviewed to determine presence of allergic-type reaction and its severity. Variables potentially indicative of allergic-type reactions were selected a priori and included allergies entered in the Veteran Affair's Allergy Reaction Tracking (ART) system (either historical [reported] or observed), allergy diagnosis codes, medications administered to treat allergic reactions, and text searches of clinical notes for keywords and phrases indicative of a potential allergic-type reaction. A model to detect allergic-type reaction events was iteratively developed on the training cohort and then applied to the test cohort. Algorithm test characteristics were assessed. Exposure: Preprocedural and postprocedural prophylactic antibiotic administration. Main Outcomes and Measures: Antibiotic allergic-type reactions. Results: The cohort of 36 344 patients included 34 703 CIED procedures with antibiotic exposures (mean [SD] age, 72 [10] years; 34 008 [98%] male patients); median duration of postprocedural prophylaxis was 4 days (IQR, 2-7 days; maximum, 45 days). The final algorithm included 7 variables: entries in the Veteran Affair's hospitals ART, either historic (odds ratio [OR], 42.37; 95% CI, 11.33-158.43) or observed (OR, 175.10; 95% CI, 44.84-683.76); PheCodes for "symptoms affecting skin" (OR, 8.49; 95% CI, 1.90-37.82), "urticaria" (OR, 7.01; 95% CI, 1.76-27.89), and "allergy or adverse event to an antibiotic" (OR, 11.84, 95% CI, 2.88-48.69); keyword detection in clinical notes (OR, 3.21; 95% CI, 1.27-8.08); and antihistamine administration alone or in combination (OR, 6.51; 95% CI, 1.90-22.30). In the final model, antibiotic allergic-type reactions were identified with an estimated probability of 30% or more; positive predictive value was 61% (95% CI, 45%-76%); and sensitivity was 87% (95% CI, 70%-96%). Conclusions and Relevance: In this retrospective cohort study of patients receiving periprocedural antibiotic prophylaxis, an algorithm with a high sensitivity to detect incident antibiotic allergic-type reactions that can be used to provide clinician feedback about antibiotic harms from unnecessarily prolonged antibiotic exposures was developed.