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This case-control study uses single-institution data to explore risk factors associated with vancomycin drug reaction with eosinophilia and systemic systems (DRESS) syndrome.

Allergists have been at the forefront of addressing the burden of unverified penicillin allergy labels. Coordinated national efforts with infectious diseases, antimicrobial stewardship experts, and pharmacy societies to advocate for formal evaluation of patient-reported penicillin allergy have resulted in improvements in delabeling efforts. Given the poorer health outcomes associated with the penicillin allergy label and the potential health benefits that can be gained with delabeling, improving access to penicillin allergy evaluation is of the utmost importance. Health disparities are widely recognized to impact all aspects of healthcare, and multilevel interventions at the patient, clinician and systems level are required to ensure equitable care delivery. Structural racism underpins many social determinants of health and is a key driver of racial and ethnic health disparities. In this Rostrum, we use a conceptual framework from the 2015 National Academy of Medicine report Improving Diagnosis in Health Care to explore how inequities are related to the evaluation of penicillin allergy. We use the National Institute on Minority Health and Health Disparities Strategies to Advance Health Disparities to elucidate areas of important study. Building upon existing efforts to address disparities in Allergy/Immunology, we highlight the urgent importance of understanding and eliminating health disparities in penicillin allergy evaluation and delabeling.

Background Health care institutions have their own “picklist” for clinicians to document adverse drug reactions (ADRs) into the electronic health record (EHR) allergy list. Whether the lack of a nationally standardized picklist impacts clinician data entries is unknown. Objectives The objective of this study was to assess the impact of defined reaction picklists on clinical documentation and, therefore, downstream analytics and clinical research using these data at two institutions. Methods ADR data were obtained from the EHRs of patients who visited the emergency department or outpatient clinics at Brigham and Women's Hospital (BWH) and University of Colorado Hospital (UCH) from 2013 to 2018. Reported drug class ADR prevalences were calculated. We investigated the reactions on each picklist and compared the top 40 reactions at each institution, as well as the top 10 reactions within each drug class. Results Of 2,160,116 patients, 640,444 (30%) had 928,973 active drug allergies. The most commonly reported drug class allergens were similar between BWH and UCH. BWH's picklist had 48 reactions, and UCH's had 160 reactions; 29 reactions were shared by both picklists. While the top four reactions overall (rash, GI upset/nausea/vomiting, hives, itching) were identical between sites, reactions by drug class exhibited greater documentation diversity. For example, while the summed prevalence of swelling-related reactions to angiotensin-converting-enzyme inhibitors was comparable across sites, swelling was represented by two terms (“swelling,” “angioedema”) at BWH but 11 terms at UCH (e.g., “swelling,” “edema,” by body locality). Conclusion The availability and granularity of reaction picklists impact ADR documentation in the EHR by health care providers; picklists may partially explain variations in reported ADRs across health care systems.

Allergic symptoms after messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines occur in up to 2% of recipients. Compared to nonallergic controls (n = 18), individuals with immediate allergic reactions to mRNA COVID-19 vaccines (n = 8) mounted lower immunoglobulin G1 (IgG1) to multiple antigenic targets in severe acute respiratory syndrome coronavirus 2 spike following vaccination, with significantly lower IgG1 to full-length spike (P = .04). Individuals with immediate allergic reactions to mRNA COVID-19 vaccines bound Fcγ receptors similarly to nonallergic controls. Although there was a trend toward an overall reduction in opsonophagocytic function in individuals with immediate allergic reactions compared to nonallergic controls, allergic patients produced functional antibodies exhibiting a high ratio of opsonophagocytic function to IgG1 titer.

PURPOSE The immunogenicity and reactogenicity of SARS-CoV-2 vaccines in patients with cancer are poorly understood. METHODS We performed a prospective cohort study of adults with solid-organ or hematologic cancers to evaluate anti–SARS-CoV-2 immunoglobulin A/M/G spike antibodies, neutralization, and reactogenicity ≥ 7 days following two doses of mRNA-1273, BNT162b2, or one dose of Ad26.COV2.S. We analyzed responses by multivariate regression and included data from 1,638 healthy controls, previously reported, for comparison. RESULTS Between April and July 2021, we enrolled 1,001 patients; 762 were eligible for analysis (656 had neutralization measured). mRNA-1273 was the most immunogenic (log10 geometric mean concentration [GMC] 2.9, log10 geometric mean neutralization titer [GMT] 2.3), followed by BNT162b2 (GMC 2.4; GMT 1.9) and Ad26.COV2.S (GMC 1.5; GMT 1.4; P < .001). The proportion of low neutralization (< 20% of convalescent titers) among Ad26.COV2.S recipients was 69.9%. Prior COVID-19 infection (in 7.1% of the cohort) was associated with higher responses ( P < .001). Antibody titers and neutralization were quantitatively lower in patients with cancer than in comparable healthy controls, regardless of vaccine type ( P < .001). Receipt of chemotherapy in the prior year or current steroids were associated with lower antibody levels and immune checkpoint blockade with higher neutralization. Systemic reactogenicity varied by vaccine and correlated with immune responses ( P = .002 for concentration, P = .016 for neutralization). In 32 patients who received an additional vaccine dose, side effects were similar to prior doses, and 30 of 32 demonstrated increased antibody titers (GMC 1.05 before additional dose, 3.17 after dose). CONCLUSION Immune responses to SARS-CoV-2 vaccines are modestly impaired in patients with cancer. These data suggest utility of antibody testing to identify patients for whom additional vaccine doses may be effective and appropriate, although larger prospective studies are needed.

After initial reports of anaphylaxis to the messenger RNA (mRNA) COVID-19 vaccines, the Centers for Disease Control and Prevention (CDC) put forth guidance stating that patients with a history of anaphylaxis to vaccine components like polyethylene glycol (PEG) should not receive the mRNA COVID-19 vaccines.1 To address this clinical challenge and decrease vaccine hesitancy, we published an approach to guide COVID-19 vaccination in high-risk allergy individuals.2-4 While the etiology of anaphylaxis to mRNA COVID-19 vaccines remains unclear, PEG continues to be an important focus.5,6 Paclitaxel contains polyoxyl-35 castor oil --a PEG derivative and structurally similar to the excipient in Pfizer-BioNTech and Moderna COVID-19 vaccines-- and docetaxel contains polysorbate 80 --the excipient in Janssen COVID-19 vaccine. Given this, we sought to assess the utility of pre-vaccine excipient skin testing (ST), risk stratification and COVID-19 vaccine tolerability in oncology patients with a history of paclitaxel or docetaxel hypersensitivity reaction (HSR).

Objective:To describe the incidence of systemic overlap and typical coronavirus disease 2019 (COVID-19) symptoms in healthcare personnel (HCP) following COVID-19 vaccination and association of reported symptoms with diagnosis of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in the context of public health recommendations regarding work exclusion.Design:This prospective cohort study was conducted between December 16, 2020, and March 14, 2021, with HCP who had received at least 1 dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine.Setting:Large healthcare system in New England.Interventions:HCP were prompted to complete a symptom survey for 3 days after each vaccination. Reported symptoms generated automated guidance regarding symptom management, SARS-CoV-2 testing requirements, and work restrictions. Overlap symptoms (ie, fever, fatigue, myalgias, arthralgias, or headache) were categorized as either lower or higher severity. Typical COVID-19 symptoms included sore throat, cough, nasal congestion or rhinorrhea, shortness of breath, ageusia and anosmia.Results:Among 64,187 HCP, a postvaccination electronic survey had response rates of 83% after dose 1 and 77% after dose 2. Report of ≥3 lower-severity overlap symptoms, ≥1 higher-severity overlap symptoms, or at least 1 typical COVID-19 symptom after dose 1 was associated with increased likelihood of testing positive. HCP with prior COVID-19 infection were significantly more likely to report severe overlap symptoms after dose 1.Conclusions:Reported overlap symptoms were common; however, only report of ≥3 low-severity overlap symptoms, at least 1 higher-severity overlap symptom, or any typical COVID-19 symptom were associated with infection. Work-related restrictions for overlap symptoms should be reconsidered.

Background Antibiotics are one of the leading causes of emergency room visits for adverse drug events, yet surveillance for antimicrobial allergy adverse events is limited and identifying true cases is challenging. As part of a larger study to improve antimicrobial use, we sought to develop and validate a tool for near real-time measurement of antimicrobial allergy adverse events. Methods An existing cohort of patients undergoing cardiac device procedures with known antimicrobial exposure was split into a development and validation set. Candidate triggers for identifying allergic reactionswere identified a priori, using disease phenotype codes “phecodes”, allergy documentation on allergy module of the electronic medical record (EMR), and keyword searches applied to clinical notes (e.g., “anaphylaxis,” “rash”), medication administration (e.g, corticosteroids alone or with antihistamines) and administrative codes (ICD-10 codes and phecodes). Cases were reviewed for presence of a true event, and the tool was iteratively updated based on chart review findings. The tool was then applied to the validation cohort and a sample of trigger-flagged and unflagged cases underwent manual review. Data were analyzed in SAS and model triggers were selected using a LASSO technique. Results Among 34,703 patients, N=431 cases underwent manual review (350 development; 120 validation), and 104 true allergy adverse events were identified. Among chart reviewed cases, the most frequently detected flags were keywords in unstructured clinical notes (35%), phecodes (26%), corticosteroid administration (15%), observed allergy documentation in EMR (14%) and reported allergy documentation in EMR (13%). The final model contained 7 triggers and had an AUC of 0.95, and a positive predictive value of 67% (Figure). The strongest predictors of true adverse events were the allergy health factors (aOR 358, 95% CI 76.3-999) and specific Phecodes (Table1). Conclusion We developed an antibiotic allergy measurement tool using structured and unstructured data that can be applied to detect antimicrobial adverse events in near-real time. This model may be applied to provide near real-time feedback to clinicians about antimicrobial allergy adverse events and may be useful for antimicrobial stewardship programs. Disclosures Westyn Branch-Elliman, MD, MMSc, DLA Piper,LLC/Medtronic: Advisor/Consultant|Gilead Pharmaceuticals: Grant/Research Support.

Penicillin allergy, the most frequently reported drug allergy, has been associated with suboptimal antibiotic therapy, increased antimicrobial resistance, increased rates of Clostridioides difficile colonization and infection, as well as extended hospital length of stay and increased cost. Although up to 10% of all patients may report penicillin allergy, most penicillin allergies are not confirmed. As such, most patients with a penicillin allergy can still safely use penicillin and related drugs following a more precise assessment. Herein, we review the current practices and unmet needs in penicillin allergy testing. The diagnostic algorithm is mostly based on a clinical history assessment followed by in vivo testing, i.e. skin test and/or drug challenge. As these tests are labour and resource intensive, there is increased interest in point-of-care penicillin allergy de-labelling solutions incorporated into Antimicrobial Stewardship Programmes including digital assessment tools. These can be locally parameterized on the basis of characteristics of target populations, incidence of specific allergies and local antibiotic usage to perform clinical risk stratification. Safely ruling out any residual risk remains essential and in vivo drug challenge and/or skin testing should be systematically encouraged. Gradual understanding and convergence of the risk stratification of the clinical presentation of penicillin allergy is enabling a wider implementation of this essential aspect of antimicrobial stewardship through digitalized decision tools and in vivo testing. More research is needed to deliver point of care in vitro diagnostic tools to democratize this de-labelling practice, which would be highly beneficial to patient care. This progress, together with better education of patients and clinicians about the availability, efficacy and safety of penicillin allergy testing, will increase the dissemination of penicillin allergy assessment as an important component of Antimicrobial Stewardship Programmes.

Reported adverse reactions to the mRNA-1273 vaccine (Spikevax, Moderna Inc) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) range from mild, local delayed cutaneous reactions to rarer, more serious reactions such as myocarditis. Here, we describe the presentation and successful treatment of delayed, localized necrotizing inflammatory myositis following a third dose of the mRNA-1273 SARS-CoV-2 vaccine. To our knowledge, this is the first report of biopsy-confirmed, delayed inflammatory myositis after administration of an mRNA-1273 SARS-CoV-2 vaccine booster.

Background Cutaneous reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but are not well characterized. Objective To evaluate the morphology and timing of cutaneous reactions after mRNA COVID-19 vaccines. Methods A provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination. Results From December 2020 to February 2021, we recorded 414 cutaneous reactions to mRNA COVID-19 vaccines from Moderna (83%) and Pfizer (17%). Delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions. Forty-three percent of patients with first-dose reactions experienced second-dose recurrence. Additional less common reactions included pernio/chilblains, cosmetic filler reactions, zoster, herpes simplex flares, and pityriasis rosea-like reactions. Limitations Registry analysis does not measure incidence. Morphologic misclassification is possible. Conclusions We report a spectrum of cutaneous reactions after mRNA COVID-19 vaccines. We observed some dermatologic reactions to Moderna and Pfizer vaccines that mimicked SARS-CoV-2 infection itself, such as pernio/chilblains. Most patients with first-dose reactions did not have a second-dose reaction and serious adverse events did not develop in any of the patients in the registry after the first or second dose. Our data support that cutaneous reactions to COVID-19 vaccination are generally minor and self-limited, and should not discourage vaccination.

Background Evidence-based guidelines are needed in the United States to improve evaluation of perioperative allergic reactions including recommendations for subsequent anesthesia. Objective To identify causative agent(s) and evaluate patients' tolerability of subsequent anesthesia in patients evaluated by Allergy/Immunology (A/I) at Massachusetts General Hospital. Methods We performed a retrospective review of patients referred to the outpatient A/I clinic for perioperative allergic reactions between October 2003 and May 2017. Patient demographics, atopic history, and prior adverse drug reactions were reviewed. Patients underwent a comprehensive evaluation with testing including skin testing (ST), drug challenges (when appropriate), tryptase level measurement, and specific IgE to latex measurement. Tolerance of subsequent procedures requiring anesthesia was assessed. Results Of 123 patients referred, 74 (60%) were female and the mean age was 46 (±18) years. At least 1 causative agent was identified in 28 patients (24%, n = 28 of 118). Seventeen of 28 (61%) patients were ST positive to an antibiotic, including 13 (46%) positive to cefazolin; 3 patients (11%) had a positive latex specific IgE. Of 85 patients who had subsequent anesthesia with a known outcome, 78 (91%) did not have another perioperative allergic reaction. Two of 5 patients with an elevated baseline tryptase level did not tolerate subsequent anesthesia. Conclusion The majority of patients safely received subsequent anesthesia after comprehensive A/I evaluation for their perioperative allergic reactions; however, improved algorithmic care is needed in the United States. Among ST-positive patients (24%), antibiotics (especially cefazolin) were the most common culprits. An elevated baseline tryptase level was associated with an increased risk of recurrent perioperative allergic reactions.

ImportanceStandardized processes for identifying when allergic-type reactions occur and linking reactions to drug exposures are limited.ObjectiveTo develop an informatics tool to improve detection of antibiotic allergic-type events.Design, Setting, and ParticipantsThis 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.ExposurePreprocedural and postprocedural prophylactic antibiotic administration.Main Outcomes and MeasuresAntibiotic allergic-type reactions.ResultsThe 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 RelevanceIn 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.

Background Penicillin and other beta-lactam antibiotics are recommended for group B Streptococcus and cesarean section prophylaxis, but approximately 10% of pregnant patients report a penicillin allergy. Objective To assess the safety and impact of penicillin allergy evaluation in pregnant patients. Methods In this retrospective study of obstetrician-ordered Allergy/Immunology (AI) electronic consultations (e-consults) from September 20, 2017 through December 31, 2019, we reviewed the electronic health record for e-consult recommendation; patient demographic, obstetric, and allergy histories; and peripartum antibiotic utilization with indication. For patients whose electronic consultation recommended an in-person AI evaluation, testing outcomes were determined, and multivariable logistic regression models were used to compare antibiotic use between patients who did and did not receive an in-person AI evaluation. Results Of 389 obstetrician-ordered e-consults, 363 (93%) recommended an in-person AI evaluation; of these, 222 (61%) patients received an in-person AI evaluation. Of 220 (99%) patients skin tested, 209 (95%) had their penicillin allergy label safely removed. Compared with patients who did not receive an in-person AI evaluation despite it being recommended (n = 141), patients with in-person AI evaluation (n = 222) had reduced peripartum vancomycin (adjusted odds ratio [aOR], 0.07; 95% CI, 0.01-0.33), clindamycin (aOR, 0.17; 95% CI, 0.08-0.34), and gentamicin (aOR, 0.39; 95% CI, 0.19-0.78) use and increased penicillin (aOR, 18.0; 95% CI, 6.30-51.2) use. The fully AI evaluated patients had increased first-line antibiotic prophylaxis for group B Streptococcus (aOR, 26.9; 95% CI, 6.32-114) and cesarean section (aOR, 1.94; 95% CI, 1.06-3.52). Conclusions In a sample of 220 pregnant patients with penicillin allergy histories and in-person AI evaluation, penicillin allergy testing was safe and associated with significantly reduced broad-spectrum antibiotic use and increased first-line beta-lactam antibiotic use.