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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.

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.

A multidisciplinary team developed a policy-based approach that provides guidance for using peer review protected information for safety research while maintaining peer review privilege. The approach includes project approval by an ad hoc review committee, signed confidentiality agreements by investigators and study staff, early removal of case identification numbers, standards for maintaining data security, and publication of aggregate data without data set sharing. By describing this procedure and embedding into an institutional policy on Data for Performance Improvement, the team encourages other institutions to develop similar policies consistent with their state regulations.

Background Having a penicillin allergy label associates with a higher risk for antibiotic resistance and increased health care use. Objective We sought to assess the accuracy of skin tests and specific IgE quantification in the diagnostic evaluation of patients reporting a penicillin/β-lactam allergy. Methods We performed a systematic review and diagnostic accuracy meta-analysis, searching on MEDLINE, Scopus, and Web of Science. We included studies conducted in patients reporting a penicillin allergy and in whom skin tests and/or specific IgE quantification were performed and compared with drug challenge results. We quantitatively assessed the accuracy of diagnostic tests with bivariate random-effects meta-analyses. Meta-regression and subgroup analyses were performed to explore causes of heterogeneity. Studies’ quality was evaluated using QUADAS-2 criteria. Results We included 105 primary studies, assessing 31,761 participants. Twenty-seven studies were assessed by bivariate meta-analysis. Skin tests had a summary sensitivity of 30.7% (95% CI, 18.9%-45.9%) and a specificity of 96.8% (95% CI, 94.2%-98.3%), with a partial area under the summary receiver-operating characteristic curve of 0.686 (I2 = 38.2%). Similar results were observed for subanalyses restricted to patients reporting nonimmediate maculopapular exanthema or urticaria/angioedema. Specific IgE had a summary sensitivity of 19.3% (95% CI, 12.0%-29.4%) and a specificity of 97.4% (95% CI, 95.2%-98.6%), with a partial area under the summary receiver-operating characteristic curve of 0.420 (I2 = 8.5%). Projected predictive values mainly reflect the low frequency of true penicillin allergy. Conclusions Skin tests and specific IgE quantification appear to have low sensitivity and high specificity. Because current evidence is insufficient for assessing the role of these tests in stratifying patients for delabeling, we identified key requirements needed for future studies.

Background Programmed cell death receptor ligand 1 (PD-L1) inhibitors are immune checkpoint inhibitors (ICIs) with a side effect profile that may differ from other classes of ICIs such as those directed against cytotoxic T-lymphocyte−associated protein 4 (CTLA-4) and programmed cell death 1 receptor (PD-1). Being the more recently approved class of checkpoint inhibitors, there are no studies investigating the frequency, etiology and predictors of acute kidney injury (AKI) in patients receiving PD-L1 inhibitors. Methods This was a retrospective cohort study of patients who received PD-L1 inhibitors during 2017 to 2018 in our healthcare system. AKI was defined by a ≥1.5-fold rise in serum creatinine from baseline. The etiology of all cases of sustained AKI (lasting >48 hours) and clinical course were determined by review of electronic health records. Results The final analysis included 599 patients. Within 12 months of ICI initiation, 104 patients (17%) experienced AKI, and 36 (6%) experienced sustained AKI; however, only 5 (, Graphical abstract

OBJECTIVES: Documentation of allergies in a coded, non-free-text format in the electronic health record (EHR) triggers clinical decision support to prevent adverse events. Health system-wide patient safety initiatives to improve EHR allergy documentation by specifically decreasing free-text allergy entries have not been reported. The goal of this initiative was to systematically reduce free-text allergen entries in the EHR allergy module. METHODS: We assessed free-text allergy entries in a commercial EHR used at a multi-hospital integrated healthcare system in the greater Boston area. Using both manual and automated methods, a multidisciplinary consensus group prioritized high risk and frequently used free-text allergens for conversion to coded entries, added new allergen entries, and deleted duplicate allergen entries. Environmental allergies were moved to the patient problem list. RESULTS: We identified 242,330 free-text entries, which included a variety of environmental allergies (42%), food allergens (18%), contrast media allergies (13%), “no known allergy” (12%), drug allergies (2%), and “no contrast allergy” (2%). The majority of free-text entries were entered by medical assistants in ambulatory settings (34%) and registered nurses in peri-operative settings (20%). We remediated a total of 52,206 free-text entries with automated methods, and 79,578 free-text entries with manual methods. CONCLUSION: Through this multidisciplinary intervention, we identified and remediated 131,784 free-text entries in our EHR to improve clinical decision support and patient safety. Additional strategies are required to completely eliminate free-text allergy entry, and establish systematic, consistent and safe guidelines for documenting allergies.

Background Allergen immunotherapy (AIT) treatment for allergic rhinitis and asthma is used by 2.6 million Americans annually. Clinical and sterility testing studies identify no risk of contamination or infection from extracts prepared using recommended aseptic techniques, but regulatory concerns persist. Social media can be used to investigate rare adverse effects not captured by traditional studies. Objective We sought to investigate large social media databases for suggestion of AIT skin and soft tissue infection (SSTI) risk and compare this risk to a comparator procedure with a sterile pharmaceutical. Methods We analyzed US-restricted data from more than 10 common text-based social media platforms including Facebook, Twitter, and Reddit between 2012 and 2016. We used natural language processing (NLP) to identify posts related to AIT and, separately, influenza vaccination (comparator procedure). NLP was followed by manual review to identify posts suggesting a possible SSTI associated with either AIT or influenza vaccination. SSTI frequencies with 95% CIs were compared. Results We identified 25,126 AIT posts, which were matched by social media platform to 25,126 influenza vaccination–related posts. NLP identified 4088 (16.3%) AIT posts that required manual review, with 6 posts (0.02%; 95% CI, 0.005%-0.043%) indicative of possible AIT-related SSTI. NLP identified 2689 (10.7%) influenza posts that required manual review, with 7 posts (0.03%; 95% CI, 0.007%-0.048%) indicative of possible influenza vaccination–related SSTI. Conclusions Social media data suggest that SSTI from AIT and influenza vaccination are equally rare events. Given that AIT's SSTI risk appears comparable to the risk using a sterile pharmaceutical based on social media data, current aseptic technique procedures seem safe.

International audience; Background: Patients with a penicillin allergy label tend to have worse clinical outcomes and increased healthcare use. Drug provocation tests (DPT) are the gold-standard in the diagnostic workup of penicillin allergy, but safety concerns may hinder their performance. We aimed to assess the frequency of severe reactions following a DPT in patients with reported allergy to penicillins or other β-lactams.Methods: We performed a systematic review, searching MEDLINE, Scopus, and Web of Science. We included primary studies assessing participants with a penicillin allergy label who underwent a DPT. We performed a Bayesian meta-analysis to estimate the pooled frequency of severe reactions to penicillin DPTs. Sources of heterogeneity were explored by subgroup and metaregression analyses.Results: We included 112 primary studies which included a total of 26,595 participants. The pooled frequency of severe reactions was estimated at 0.06% (95% credible interval [95% CrI] = 0.01%-0.13%; I2 = 57.9%). Most severe reactions (80/93; 86.0%) consisted of anaphylaxis. Compared to studies where the index reaction was immediate, we observed a lower frequency of severe reactions for studies assessing non-immediate index reactions (OR = 0.05; 95% CrI = 0-0.31). Patients reporting anaphylaxis as their index reaction were found to be at increased risk of developing severe reactions (OR = 13.5; 95% CrI = 7.7-21.5; I2 = 0.3%). Performance of direct DPTs in low-risk patients or testing with the suspected culprit drug were not associated with clinically relevant increased risk of severe reactions.Conclusions: In patients with a penicillin allergy label, severe reactions resulting from DPTs are rare. Therefore, except for patients with potentially life-threatening index reactions or patients with positive skin tests-who were mostly not assessed in this analysis -, the safety of DPTs supports their performance in the diagnostic assessment of penicillin allergy.

Vancomycin Infusion Reaction Although “red man” might, at first glance, be taken as a straightforward description of a white male patient with an erythematous skin reaction, the term had a ready re...

The U.S. Food and Drug Administration (FDA) has recently issued an Emergency Use Authorization (EUA) for 2 highly effective coronavirus disease 2019 (COVID-19) vaccines from Pfizer-BioNTech and Moderna. This has brought hope to millions of Americans in the midst of an ongoing global pandemic. The FDA EUA guidance for both vaccines is to not administer the vaccine to individuals with a known history of a severe allergic reaction (eg, anaphylaxis) to any component of the COVID-19 vaccine. The Centers for Disease Control and Prevention (CDC) additionally advises individuals with a history of an immediate allergic reaction to a vaccine or injectable or any history of anaphylaxis be observed for 30 minutes after COVID-19 vaccination. All other individuals should be observed for 15 minutes after COVID-19 vaccination. Staff at vaccine clinics must be able to identify and manage anaphylaxis. Post–FDA EUA, despite very strong safety signals in both phase 3 trials, reports of possible allergic reactions have raised public concern. To provide reassurance and support during widespread global vaccination, allergists must offer clear guidance to individuals based on the best information available, but also in accordance with the broader recommendations of regulatory agencies. This review summarizes vaccine allergy epidemiology and proposes drug and vaccine allergy expert opinion informed risk stratification for Allergy specialist use in conjunction with guidance of public health and regulatory authorities. The risk stratification schema guide care for (1) individuals with different allergy histories to safely receive their first mRNA COVID-19 vaccine and (2) individuals who develop a reaction to their first dose of mRNA COVID-19 vaccine.

Importance Cefazolin is the preoperative antibiotic of choice because it is safer and more efficacious than second-line alternatives. Surgical patients labeled as having penicillin allergy are less likely to prophylactically receive cefazolin and more likely to receive clindamycin or vancomycin, which results in higher rates of surgical site infections. Objective To examine the incidence of dual allergy to cefazolin and natural penicillins. Data Sources MEDLINE/PubMed, Web of Science, and Embase were searched without language restrictions for relevant articles published from database inception until July 31, 2020. Study Selection In this systematic review and meta-analysis, a search of MEDLINE/PubMed, Web of Science, and Embase was performed for articles published from database inception to July 31, 2020, for studies that included patients who had index allergies to a natural penicillin and were tested for tolerability to cefazolin or that included patients who had index allergies to cefazolin and were tested for tolerability to a natural penicillin. A total of 3228 studies were identified and 2911 were screened for inclusion. Data Extraction and Synthesis Data were independently extracted by 2 authors. Bayesian meta-analysis was used to estimate the frequency of allergic reactions. Main Outcomes and Measures Dual allergy to cefazolin and a natural penicillin. Results Seventy-seven unique studies met the eligibility criteria, yielding 6147 patients. Cefazolin allergy was identified in 44 participants with a history of penicillin allergy, resulting in a dual allergy meta-analytical frequency of 0.7% (95% credible interval [CrI], 0.1%-1.7%;I2 = 74.9%). Such frequency was lower for participants with unconfirmed (0.6%; 95% CrI, 0.1%-1.3%;I2 = 54.3%) than for those with confirmed penicillin allergy (3.0%; 95% CrI, 0.01%-17.0%;I2 = 88.2%). Thirteen studies exclusively assessed surgical patients (n = 3884), among whom 0.7% (95% CrI, 0%-3.3%;I2 = 85.5%) had confirmed allergy to cefazolin. Low heterogeneity was observed for studies of patients with unconfirmed penicillin allergy who had been exposed to perioperative cefazolin (0.1%; 95% CrI, 0.1%-0.3%;I2 = 13.1%). Penicillin allergy was confirmed in 16 participants with a history of cefazolin allergy, resulting in a meta-analytical frequency of 3.7% (95% CrI, 0.03%-13.3%;I2 = 64.4%). The frequency of penicillin allergy was 4.4% (95% CrI, 0%-23.0%;I2 = 75%) for the 8 studies that exclusively assessed surgical patients allergic to cefazolin. Conclusions and Relevance These findings suggest that most patients with a penicillin allergy history may safely receive cefazolin. The exception is patients with confirmed penicillin allergy in whom additional care is warranted.

Delayed Local Reactions to mRNA-1273 Vaccine Delayed cutaneous reactions developed in 12 patients days after initial injection-related symptoms resolved. The reactions, some as severe as grade 3, r...

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents our greatest hope to combat the devastating coronavirus disease 2019 (COVID-19) pandemic. Amid ongoing global vaccination efforts, rare cases of severe allergic reactions to COVID-19 mRNA vaccines have received significant attention. Although the exact nature of these reactions may be heterogeneous, various approaches exist to engage with patients, communities, public health departments, primary care providers, and other clinicians in a multidisciplinary approach to advance population health. Whereas it is optimal for patients to receive COVID-19 vaccination as outlined in emergency use authorizations, second-dose deferral of mRNA vaccines may be a consideration within a shared decision-making paradigm of care in select circumstances characterized by high durable first-vaccine-dose protection and significant elevations of vaccine anaphylaxis risk. Still, the durability of protection afforded by a single dose of a COVID-19 mRNA vaccine is uncertain, and alternative approaches to complete vaccination, including precautionary use of a COVID-19 viral vector vaccine, also remain patient-preference-sensitive options. There is an urgent need to define correlates of COVID-19 immunity and the level of longer-term protection afforded by COVID-19 vaccination.

ObjectiveThe evidence pertaining to the effects of asthma on Coronavirus disease 2019 outcomes has been unclear. To improve our understanding of the clinically important association of asthma and Coronavirus disease 2019.MethodsA matched cohort study was performed using data from the Mass General Brigham Health Care System (Boston, MA). Adult (age ≥ 18 years) patients with confirmed Coronavirus disease 2019 and without chronic obstructive pulmonary disease, cystic fibrosis, or interstitial lung disease between March 4, 2020 and July 2, 2020 were analyzed. Up to 5 non-asthma comparators were matched to each asthma patient based on age (within 5 years), sex, and date of positive test (within 7 days). The primary outcomes were hospitalization, mechanical ventilation, and death, using multivariable Cox-proportional hazards models accounting for competing risk of death, when appropriate. Patients were followed for these outcomes from diagnosis of Coronavirus disease 2019 until July 2, 2020.ResultsAmong 562 asthma patients, 199 (21%) were hospitalized, 15 (3%) received mechanical ventilation, and 7 (1%) died. Among the 2686 matched comparators, 487 (18%) were hospitalized, 107 (4%) received mechanical ventilation, and 69 (3%) died. The adjusted Hazard Ratios among asthma patients were 0.99 (95% Confidence Internal 0.80, 1.22) for hospitalization, 0.69 (95% Confidence Internal 0.36, 1.29) for mechanical ventilation, and 0.30 (95% Confidence Internal 0.11, 0.80) for death.ConclusionsIn this matched cohort study from a large Boston-based healthcare system, asthma was associated with comparable risk of hospitalization and mechanical ventilation but a lower risk of mortality.

International audience

Alternative antibiotics for surgical prophylaxis are associated with increased adverse events and surgical site infection compared to cefazolin. In a sample of perioperative inpatients from 100 hospitals in the United States, cefazolin was 9-fold less likely to be used in patients with a documented β-lactam allergy whereas clindamycin was 45-fold more likely.

It has been over 75 years since the first use of penicillin and the first description of penicillin-associated hypersensitivity reactions...

Background Drug allergy is frequently reported, but uncommonly confirmed with diagnostic testing. Although drug allergy assessments can improve clinical care, patient concerns may impact the optimal diagnostic approach and/or the clinical effectiveness of diagnostic testing. Objective To assess drug allergy patient concerns. Methods Using data from a multisite, prospective longitudinal cohort study, the United States Drug Allergy Registry (January 16, 2019, to January 24, 2020), we determined patient self-reported characteristics and qualitatively coded free-text patient concerns about their drug allergy/allergies. We assessed associations between patient characteristics and drug allergy concerns using multinomial logistic regression models. Results Of 592 patients (mean age, 49 [standard deviation, 17] years, 74% female, 88% white), the most commonly reported drug allergies were penicillins (78%), cephalosporins (12%), and sulfonamides (12%) with common reactions of rash (62%), hives (54%), itching (48%), flushing or facial redness (28%), and swelling or angioedema (24%). Patient concerns, coded from free text, were optimal medication use (41%), no concern (17%), allergic reaction (14%), diagnosis (12%), and severe allergic reaction (12%). Using multinomial regression, the presence of drug allergy concerns increased with greater age, higher number of reported drug reactions, more antibiotic use, and certain reaction symptoms, most notably mouth or palate itching. Female sex was associated with increased severe allergic reaction concern. Poorer general and mental health was associated with increased allergic reaction concern. Conclusion Patients with drug allergy were concerned about their options for medical treatment, having an allergic reaction, and receiving clarity about their diagnosis. Capturing and addressing patient concerns may improve the approach to patients with drug allergy and/or the effectiveness of drug allergy testing.

Background Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but severe hypersensitivity reaction that remains poorly characterized in the United States. Objective To identify and describe DRESS syndrome cases in an integrated health care system using electronic health record (EHR) allergy module free-text searches. Methods We identified DRESS syndrome cases with rash, absolute eosinophil count of 500/L or more, organ involvement, and a European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples score of 2 or more by reviewing those patients from 1980 to 2016 whose EHR allergic reaction matched DRESS-related key words. Liver injury required alanine aminotransferase level of 100 U/L or more, and renal injury required creatinine increase by 0.5 mg/dL (or 50%) or more. Patient and DRESS characteristics were described, resource use was determined, and cost was estimated. Results Among 3,162,562 patients with 3,319,387 million allergy entries, 538 reactions matched key words, and 69 were DRESS syndrome cases (prevalence 2.18 per 100,000). Patients with DRESS had liver (42%) or renal (42%) injury; 11 (16%) had both liver and renal injury. Primary drug culprits were antibiotics (74%) (vancomycin [39%], β-lactams [23%], fluoroquinolones [4%], tetracyclines [4%], and sulfonamides [3%]) and anticonvulsants (20%). Of 65 (94%) hospitalized patients with DRESS, 43 (66%) were hospitalized for DRESS syndrome management with median length of stay of 9 days (interquartile range, 6-17 days) and cost approximately $17,101 per patient. Conclusions Using free-text search of the EHR allergy module identified a large US DRESS syndrome cohort. DRESS prevalence was 2.18 per 100,000 patients. Both liver and kidney injury were frequent, and vancomycin was the most common drug culprit. DRESS cases were morbid and resource-intensive.

Background Vancomycin, the most common antimicrobial used in US hospitals, can cause diverse adverse reactions, including hypersensitivity reactions (HSRs). Yet, little is known about vancomycin reactions documented in electronic health records. Objective To describe vancomycin HSR epidemiology from electronic health record allergy data. Methods This was a cross-sectional study of patients with 1 or more encounter from 2017 to 2019 and an electronic health record vancomycin drug allergy label (DAL) in 2 US health care systems. We determined prevalence and trends of vancomycin DALs and assessed active DALs by HSR phenotype determined from structured (coded) and unstructured (free-text) data using natural language processing. We investigated demographic associations with documentation of vancomycin red man syndrome (RMS). Results Among 4,490,618 patients, 14,426 (0.3%) had a vancomycin DAL with 18,761 documented reactions (2,248 [12.0%] free-text). Quarterly mean vancomycin DALs added were 253 ± 12 and deleted were 12 ± 2. Of 18,761 vancomycin HSRs, 7,903 (42.1%) were immediate phenotypes and 3,881 (20.7%) were delayed phenotypes. Common HSRs were rash (32% of HSRs) and RMS (16% of HSRs). Anaphylaxis was coded in 6% cases of HSRs. Drug reaction eosinophilia and systemic symptoms syndrome was the most common coded vancomycin severe cutaneous adverse reaction. RMS documentation was more likely for males (odds ratio, 1.30; 95% CI, 1.17-1.44) and less likely for blacks (odds ratio, 0.59; 95% CI, 0.47-0.75). Conclusions Vancomycin causes diverse adverse reactions, including common (eg, RMS) and severe (eg, drug reaction eosinophilia and systemic symptoms syndrome) reactions entered as DAL free-text. Anaphylaxis comprised 6% of documented vancomycin HSRs, although true vancomycin IgE-mediated reactions are exceedingly rare. Improving vancomycin DAL documentation requires more coded entry options, including a coded entry for RMS.

OBJECTIVES: Over 90% of patients who report a penicillin allergy have the allergy disproved when tested. Unnecessary use of alternative (non-beta-lactam) antibiotics can result in more treatment failures and adverse reactions. We described the prevalence and impact of a reported penicillin allergy in high-cost high-need (HCHN) patients. STUDY DESIGN: Retrospective cohort. METHODS: We identified HCHN patients in a care management program of an urban academic medical center (01/01/2014–12/31/2016). We used multivariable logistic regression models to determine the association between a reported penicillin allergy and antibiotic use. We used multivariable Poisson regression models to determine the association between a reported penicillin allergy, with or without multiple drug intolerance syndrome (≥3 reported drug allergies), and healthcare utilization. RESULTS: Of 1,870 HCHN patients, 383 (20%) reported penicillin allergy, 835 (45%) had multiple drug intolerance syndrome, and 290 (16%) had both. HCHN patients reporting penicillin allergy had an increased odds of beta-lactam alternative antibiotic use (adjusted Odds Ratio ([aOR] 3.84 [95%CI 2.17, 6.80]). Healthcare utilization was significantly higher for patients reporting a penicillin allergy alone (adjusted relative risk [aRR] 1.13 [95% CI 1.03, 1.25]), and with concurrent multiple drug intolerance syndrome (aRR 1.20 [95% CI 1.08, 1.34]). CONCLUSIONS: HCHN patients had a high burden of reported drug allergy. A reported penicillin allergy conferred a 4-fold increased odds of beta-lactam alternative antibiotic use. Reporting penicillin allergy, with and without multiple drug intolerance syndrome, was associated with significantly more healthcare utilization. HCHN care management programs should consider systematic drug allergy evaluations to optimize antibiotic use in these fragile patients.

Background The epidemiology of multiple drug intolerance syndrome (MDIS) and multiple drug allergy syndrome (MDAS) is poorly characterized. We used electronic health record (EHR) data to describe prevalences of MDIS and MDAS and to examine associations with anxiety and depression. Methods Patients with ≥3 outpatient encounters at Partners HealthCare System from 2008 to 2015 were included. Patients with MDIS had intolerances to ≥3 drug classes, and patients with MDAS had hypersensitivities to ≥2 drug classes. Psychiatric conditions and comorbidities were defined from the EHR and used in multivariable logistic regression models to assess the relation between anxiety/depression and MDIS/MDAS. Results Of 746 888 patients, 47 634 (6.4%) had MDIS and 8615 (1.2%) had MDAS; 3171 (0.4%) had both. Anxiety (adjusted odds ratio [aOR] 1.72 [1.65, 1.80]), depression (aOR 1.46 [1.41, 1.52]), and both anxiety and depression (aOR 1.97 [1.86, 2.08]) were associated with increased odds of MDIS. Depression was associated with increased odds of MDAS (aOR 1.41 [1.28, 1.56]), but there were no clear associations with anxiety (aOR 1.13 [0.99, 1.30]) nor both depression and anxiety (aOR 1.13 [0.92, 1.38]). Conclusion While 6% of patients had MDIS, only 1% had MDAS. MDIS was associated with both anxiety and depression; patients with both anxiety and depression had an almost twofold increased odds of MDIS. MDAS was associated with a 40% increased odds of depression, but there was no significant association with anxiety. Psychological assessments may be useful in the evaluation and treatment of patients with MDIS and MDAS; physiologic causes for MDAS warrant further investigation.

Background Critical limb ischemia (CLI) is a feared complication of peripheral vascular disease that often requires surgical management and may require amputation of the affected limb. We developed a decision model to inform clinical management for a 63-year-old woman with CLI and multiple medical comorbidities, including advanced heart failure and diabetes. Methods We developed a Markov decision model to evaluate 4 strategies: amputation, surgical bypass, endovascular therapy (e.g. stent or revascularization), and medical management. We measured the impact of parameter uncertainty using 1-way, 2-way, and multiway sensitivity analyses. Results In the base case, endovascular therapy yielded similar discounted quality-adjusted life months (26.50 QALMs) compared with surgical bypass (26.34 QALMs). Both endovascular and surgical therapies were superior to amputation (18.83 QALMs) and medical management (11.08 QALMs). This finding was robust to a wide range of periprocedural mortality weights and was most sensitive to long-term mortality associated with endovascular and surgical therapies. Utility weights were not stratified by patient comorbidities; nonetheless, our conclusion was robust to a range of utility weight values. Conclusions For a patient with CLI, endovascular therapy and surgical bypass provided comparable clinical outcomes. However, this finding was sensitive to long-term mortality rates associated with each procedure. Both endovascular and surgical therapies were superior to amputation or medical management in a range of scenarios.

Background Angiotensin-converting enzyme inhibitors (ACEIs) are a common cause of drug-induced angioedema in the United States. Most epidemiologic ACEI angioedema data are from large multicenter clinical trials. Objective The objective of this study was to identify the incidence of and risk factors for ACEI angioedema using a large integrated electronic health record (EHR). Methods We conducted a retrospective cohort study of all ACEI prescriptions in the outpatient setting of a large academic center between January 1, 2000, and September 30, 2008. We determined frequency, timing, and risk factors for ACEI angioedema within 5 years of prescription. All data were derived from EHR sources, with angioedema defined by EHR reactions of angioedema, swelling, edema, or lip, eye, face, tongue, throat or mouth swelling. Results Among 134,945 patients prescribed an ACEI, 0.7% (n = 888) developed angioedema during the subsequent 5 years. Sex was similar but patients who developed ACEI angioedema were younger (61.5 vs 62.7 years, P = .007). Patients with ACEI angioedema were more likely to have a history of nonsteroidal anti-inflammatory drug allergy compared with patients who did not develop angioedema (7.1% vs 4.2%, P Conclusions The incidence of ACEI angioedema within a large EHR is consistent with large clinical trial data. We observed a persistent and relatively constant annual risk; however, angioedema risk factors and underlying genetic and pathophysiological mechanisms require further study.

BackgroundHaving a penicillin allergy label is associated with the use of less appropriate and more expensive antibiotics and increased healthcare utilization. Penicillin allergy testing results in delabeling most allergy claimants and may be cost-saving. This study aimed to project whether penicillin allergy testing in patients reporting a penicillin allergy is cost-saving.MethodsIn this economic evaluation study, we built decision models to project the economic impact of 2 strategies for a patient with a penicillin allergy label: (1) perform diagnostic testing (drug challenges, with or without skin tests); and (2) do not perform diagnostic testing. The health service perspective was adopted, considering costs with penicillin allergy tests, and with hospital bed-days/outpatient visits, antibiotic use, and diagnostic testing. Twenty-four base case decision models were built, accounting for differences in the diagnostic workup, setting (inpatient vs outpatient) and geographic region. Uncertainty was explored via probabilistic sensitivity analyses.ResultsPenicillin allergy testing was cost-saving in all decision models built. For models assessing the performance of both skin tests and drug challenges, allergy testing resulted in average savings (in United States [US] dollars) of $657 for inpatients (US: $1444; Europe: $489) and $2746 for outpatients (US: $256; Europe: $6045). 75% of simulations obtained through probabilistic sensitivity analysis identified testing as the less costly option.ConclusionsPenicillin allergy testing was projected to be cost-saving across different scenarios. These results are devised to inform guidelines, supporting the adoption of policies promoting widespread testing of patients with a penicillin allergy label.

Objective To determine the potential association between physician gender and academic advancement among US rheumatologists. Methods We performed a nationwide, cross-sectional study of all rheumatologists practicing in the US in 2014 using a comprehensive database of all licensed physicians. Among academic rheumatologists, we estimated gender differences in faculty rank, adjusting for differences in physician age, years since residency graduation, publications, National Institutes of Health (NIH) grants, registered clinical trials, and appointment at a top 20 medical school using a multivariate logistic regression model. We also estimated gender differences in leadership positions (i.e., division director and fellowship program director). Results Among 6,125 total practicing rheumatologists, 941 (15%) had academic faculty appointments in 2014. Women academic rheumatologists (41.4%) were younger and had completed residency more recently than men. Women had fewer total publications, publications on which they were the first or last author, and NIH grants. In fully adjusted analyses, women were less likely to be full or associate professors than men, with an adjusted odds ratio (OR) of 0.78 (95% confidence interval [95% CI] 0.62-0.99]). Women in rheumatology had similar odds as men of being a fellowship program director or division director (adjusted OR 0.99 [95% CI 0.69-1.43] and adjusted OR 0.96 [95% CI 0.66-1.41], respectively). Conclusion Among academic rheumatologists, women are less likely than men to be full or associate professors but have similar odds of being fellowship program directors or division directors, when adjusting for several factors known to influence faculty promotion. These differences suggest barriers to academic promotion despite representation in leadership positions within rheumatology divisions.

BACKGROUND: Cefazolin is the first-line prophylactic antibiotic used to prevent surgical site infections (SSIs) in cardiac surgery. Patients with a history of penicillin allergy often receive less effective second-line antibiotics, which is associated with an increased SSI risk. OBJECTIVE: We aimed to describe the impact of pre-operative penicillin allergy evaluation on peri-operative cefazolin use in cardiac surgery patients. METHODS: We performed a retrospective cohort study of patients with a documented penicillin allergy who underwent cardiac surgery at the Massachusetts General Hospital from September 2015 through December 2018. We describe penicillin allergy evaluation assessment and outcomes. We evaluated the relation between preoperative penicillin allergy evaluation and first-line peri-operative antibiotic use using a multivariable logistic regression model. RESULTS: Of 3,802 cardiac surgical patients, 510 (13%) had a documented penicillin allergy; 165 (33%) were referred to Allergy/Immunology. Of 160 (31%) patients who underwent penicillin allergy evaluation (i.e., penicillin skin testing and, if negative, an amoxicillin challenge), 154 (97%) were found not to have a penicillin allergy. Patients who underwent pre-operative penicillin allergy evaluation were more likely to receive the first-line peri-operative antibiotic (92% vs 38%, p < 0.001). After adjusting for potential confounders, patients who underwent pre-operative penicillin allergy evaluation had higher odds of first-line peri-operative antibiotic use (adjusted odds ratio 26.6 [95% CI: 12.8, 55.2]). CONCLUSION: Integrating penicillin allergy evaluation into routine pre-operative care ensured that almost all cardiac surgery patients evaluated received first-line antibiotic prophylaxis, a critical component of SSI risk reduction. Further efforts are needed to increase access to pre-operative allergy evaluation.

Background: Facilitating beta-lactam antibiotic use in patients reporting beta-lactam allergies in acute care settings is important to individual patient outcomes and public health; however, few initiatives have targeted the Emergency Department (ED) setting. Methods: We implemented pathways for patients reporting prior penicillin and/or cephalosporin hypersensitivity as part of a hospital guideline in the ED of a large academic medical center in the United States. We described beta-lactam test doses, pathway compliance, hypersensitivity reactions (HSRs), and allergy record updating associated with ED-administered beta-lactam test doses from October 2016 to June 2018. Results: 310 beta-lactam antibiotic test doses were administered to patients with penicillin and/or cephalosporin allergy histories in the study period (average volume 15/month [standard deviation 4]). Test doses were to cephalosporins (85%), penicillins (12%), and carbapenems (4%). 219 (71%) of test doses were compliant with the pathways. Ten patients (3.2%; 95% CI 1.6%–5.9%) had HSRs; five HSR patients (50%) had beta-lactams administered that were not pathway compliant. The allergy record was updated in 146 (47%) of patients, with improvement over the study period (p

Background Allergic drug reaction epidemiologic data are sparse because it remains difficult to identify true cases in large data sets using manual chart review. Objective To develop and validate a novel informatics method based on natural language processing (NLP) in combination with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes that identifies allergic drug reactions in the electronic health record. Methods Previously studied and high-yield ICD-9-CM codes were used to screen for possible allergic drug reactions among all inpatients admitted in 2007 and 2008. A random sample was selected for manual chart review to identify true cases of allergic drug reactions. A rule-based NLP algorithm was then developed to identify allergic drug reactions using free-text clinical notes and discharge summaries from the filtered cases. The performance of using manual chart review of ICD-9-CM codes alone was compared with ICD-9-CM codes in combination with NLP. Results Of 3907 cases identified by ICD-9-CM codes, 725 (19%) were randomly selected for manual chart review; 335 were confirmed as allergic drug reactions, resulting in a positive predictive value (PPV) of 46% (range: 18%-79%) when using ICD-9-CM codes alone. Our NLP algorithm in combination with ICD-9-CM codes achieved a PPV of 86% (range: 69%-100%). Among the 335 confirmed positive cases, NLP identified 259 true cases, resulting in a recall/sensitivity of 77% (range: 26%-100%). Among the 390 negative cases, NLP achieved a specificity of 89% (range: 69%-100%). Conclusion Using NLP with ICD-9-CM codes improved identification of allergic drug reactions. The resulting decrease in manual chart review effort will facilitate large epidemiology studies of this understudied area.

Cephalosporins are commonly used antibiotics both in hospitalized patients as well as outpatients. Hypersensitivity reactions to cephalosporins are becoming increasingly common with a wide range of immunopathologic mechanisms. Cephalosporins are one of the leading causes for perioperative anaphylaxis and severe cutaneous adverse reactions. Patients allergic to cephalosporins tend to tolerate cephalosporins with disparate R1 side chains but may react to other beta-lactams with common R1 side chains. Skin testing for cephalosporins has not been well-validated but appears to have a good negative predictive value for cephalosporins with disparate R1 side chains. In vitro tests including basophil activation tests have lower sensitivity when compared to skin testing. Rapid drug desensitization procedures are safe and effective and have been utilized successfully for immediate and some nonimmediate cephalosporin reactions. Many gaps in knowledge still exist regarding cephalosporin hypersensitivity.

Objective:To assess the safety of, and subsequent allergy documentation associated with, an antimicrobial stewardship intervention consisting of test-dose challenge procedures prompted by an electronic guideline for hospitalized patients with reported β-lactam allergies.Design:Retrospective cohort study.Setting:Large healthcare system consisting of 2 academic and 3 community acute-care hospitals between April 2016 and December 2017.Methods:We evaluated β-lactam antibiotic test-dose outcomes, including adverse drug reactions (ADRs), hypersensitivity reactions (HSRs), and electronic health record (EHR) allergy record updates. HSR predictors were examined using a multivariable logistic regression model. Modification of the EHR allergy record after test doses considered relevant allergy entries added, deleted, and/or specified.Results:We identified 1,046 test-doses: 809 (77%) to cephalosporins, 148 (14%) to penicillins, and 89 (9%) to carbapenems. Overall, 78 patients (7.5%; 95% confidence interval [CI], 5.9%–9.2%) had signs or symptoms of an ADR, and 40 (3.8%; 95% CI, 2.8%–5.2%) had confirmed HSRs. Most HSRs occurred at the second (ie, full-dose) step (68%) and required no treatment beyond drug discontinuation (58%); 3 HSR patients were treated with intramuscular epinephrine. Reported cephalosporin allergy history was associated with an increased odds of HSR (odds ratio [OR], 2.96; 95% CI, 1.34–6.58). Allergies were updated for 474 patients (45%), with records specified (82%), deleted (16%), and added (8%).Conclusion:This antimicrobial stewardship intervention using β-lactam test-dose procedures was safe. Overall, 3.8% of patients with β-lactam allergy histories had an HSR; cephalosporin allergy histories conferred a 3-fold increased risk. Encouraging EHR documentation might improve this safe, effective, and practical acute-care antibiotic stewardship tool.

Allergic condition management more often requires allergist guidance than allergy testing; necessary testing may be unavailable at initial drug allergy consultations. Electronic consultations (e-consults) provide expedited, problem-focused, potentially cost-saving care in other medical specialties, but have not yet been studied in Allergy/Immunology.To describe e-consult use at an academic allergy/immunology practice.E-consult data (August 10, 2016 through July 31, 2018) and in-person consult data (August 1, 2014 through July 31, 2018) were reviewed to determine consult volume, outcomes, indications, and timing. Referral reasons and wait times were compared with chi-square tests.E-consults grew from 1% to 10% of all new consults, with concurrent growth in in-person consults. Of 306 completed e-consults, 41 (13.4%) made diagnostic, therapeutic, or alternative referral recommendations, with 30 (73%) recommendations followed; 183 (59.8%) patients required an in-person Allergy/Immunology consult, and only 5 (2%) patients saw an allergist without an e-consult recommendation to do so. E-consults were used more often than in-person consults for adverse drug reactions (66% vs 9%; P.001), especially penicillin allergy (132, 61% of all e-consults) and immunodeficiency (15% vs 2%; P.001). Allergists completed e-consults in a median of 11 minutes, with a median turnaround time of 22 hours. E-consult implementation was associated with a decreased median in-person consult wait time (1.5 fewer calendar days; P.05).E-consults were increasingly used, particularly for historical adverse drug reactions and immunodeficiency. Implementation of an e-consult program resulted in decreased in-person wait times despite an increase in overall consult volume, supporting this model's ability to provide expedited, problem-focused care.

Background Treatment guidelines for pneumonia recommend beta-lactam antibiotic-based therapy. Although reported penicillin allergy is common, more than 90% of patients with reported penicillin allergy are not allergic. Objective We evaluated the association of a documented penicillin and/or cephalosporin (P/C) allergy to antibiotic use for the treatment of inpatient pneumonia. Methods This was a national cross-sectional study conducted among Vizient, Inc., network hospitals that voluntarily contributed data. Among hospitalized patients with pneumonia, we examined the relation of a documented P/C allergy in the electronic health record to prevalence of first-line beta-lactam antibiotic administration and alternative antibiotics using multivariable log-binomial regression with generalized estimating equations. Results Of 2,276 inpatients receiving antibiotics for pneumonia at 95 U.S. hospitals, 450 (20%) had a documented P/C allergy. Compared with pneumonia patients without a documented P/C allergy, patients with a documented P/C allergy had reduced prevalence of first-line beta-lactam antibiotic use (adjusted prevalence ratio [aPR] 0.79; 95% confidence interval [95% CI] 0.69-0.89]). Patients with high-risk P/C reactions (n = 91) had even lower prevalence of first-line beta-lactam antibiotic use (aPR 0.47; 95% CI 0.35-0.64). Alternative antibiotics associated with a higher use in pneumonia patients with a documented P/C allergy included carbapenems (aPR 1.61; 95% CI 1.22-2.13) and fluoroquinolones (aPR 1.52; 95% CI 1.21-1.91). Conclusions Inpatients with documented P/C allergy and pneumonia were less likely to receive recommended beta-lactams and more likely to receive carbapenems and fluoroquinolones. Inpatient allergy assessment may improve optimal antibiotic therapy for the 20% of inpatients with pneumonia and a documented P/C allergy.

This study examines the incidence of acute allergic reactions to mRNA COVID-19 vaccine administrations in health care employees in Massachusetts.

Background Ceftaroline fosamil is a cephalosporin approved for treating skin and soft tissue infections (SSTIs), including those caused by methicillin-resistant Staphylococcus aureus and community-acquired pneumonia (CAP). Objectives We aimed to study ceftaroline use and associated adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs), among inpatients. Methods We performed a retrospective electronic health record review of inpatients from Massachusetts General Hospital and Brigham and Women's Hospital who received ceftaroline between May 2012 and February 2015. ADRs diagnosed by clinical providers during the course of clinical care were subsequently verified and classified. Risk factors for ADRs were identified. Results Among 96 patients (median age, 57 years; 54% females) who received a median of 28 (interquartile range, 6-63) ceftaroline doses, 54% were being treated for methicillin-resistant Staphylococcus aureus and treatment indications other than SSTI and CAP comprised 59% of care. There were 31 ADRs observed in 20 (21%) patients; hematologic (n = 15) and cutaneous (n = 9) findings were most common. Observed HSRs included rash with mucosal lesions (n = 1), rash with skin desquamation (n = 1), and possible organ-specific HSRs (n = 2). Patients who suffered an ADR received more doses of ceftaroline (median, 46 vs 21; P = .013). There was no increased risk of ceftaroline ADR among patients with reported beta-lactam allergy history ( P > .5). Conclusions Ceftaroline is used to treat a range of infections beyond SSTI and CAP. We observed a high rate of ADRs from ceftaroline, including signs of severe HSRs. More data are needed to understand the frequency and predictors of ceftaroline ADRs and HSRs.

Background Hypersensitivity reactions (HSRs) during the perioperative period are unpredictable and can be life threatening. Prospective studies for the evaluation of perioperative HSRs are lacking, and data on causative agents vary between different studies. Objective The objective of this study was to prospectively determine the success of a comprehensive allergy evaluation plan for patients with HSRs during anesthesia, including identification of a causative agent and outcomes during subsequent anesthesia exposure. Methods All patients referred for a perioperative HSR between November 2013 and March 2015, from a Boston teaching hospital, were evaluated using a standardized protocol with skin testing (ST) within 6 months of HSR. Comprehensive allergy evaluation included collection of patient information, including characteristics of HSR during anesthesia. We reviewed the results of ST and/or test doses for all potential causative medications Event-related tryptase levels were reviewed when available. Results Over 17 months, 25 patients completed the comprehensive allergy evaluation. Fifty-two percent (13 of 25) were female with a median age of 52 (interquartile range 43-66) years. The most frequently observed HSR systems were cutaneous (68%), cardiovascular (64%), and pulmonary (24%). A culprit drug, defined as a positive ST, was identified in 36% (9 of 25) of patients. The most common agent identified was cefazolin (6 of 9). After our comprehensive evaluation and management plan, 7 (7 of 8, 88%) patients tolerated subsequent anesthesia. Conclusions Cefazolin was the most commonly identified cause of a perioperative HSR in our study population. Skin testing patients within 6 months of a perioperative HSR may improve the odds of finding a positive result. Tolerance of subsequent anesthesia is generally achieved in patients undergoing our comprehensive evaluation.

Background Vancomycin is a broad-spectrum antibiotic whose use may be limited by adverse drug reactions (ADRs). Although vancomycin toxic effects are known, there are limited data on vancomycin hypersensitivity reactions (HSRs). Objective To understand the most commonly reported vancomycin HSRs through systematic case review. Methods We performed a literature search for English-language case reports and series from 1982 through 2015 (last search July 31, 2015) on Ovid MEDLINE and PubMed. The search included the subject heading vancomycin with the subheading adverse effects and separate text searches for vancomycin with a list of specified HSRs. References of identified articles were reviewed to find additional articles. Clinical data were collected and summarized. Results Of 201 identified articles, 84 were screened and 57 fully assessed; these 57 articles contained 71 vancomycin HSR cases that were included in analysis. Vancomycin HSRs were immediate (anaphylaxis, n = 7) and nonimmediate (n = 64). Nonimmediate HSRs included linear IgA bullous dermatosis (LABD, n = 34), drug rash eosinophilia and systemic symptoms (DRESS) syndrome (n = 16), acute interstitial nephritis (AIN, n = 8), and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN, n = 6). Median times of vancomycin therapy before HSR onset was 7 days (interquartile range [IQR], 4–10 days) for LABD, 9 days (IQR, 9–22 days) for SJS/TEN, 21 days (IQR, 17–28 days) for DRESS syndrome, and 26 days (IQR, 7–29 days) for AIN. Overall, 11 patients (16%) died, and 4 (6%) had deaths attributed to the HSR. Conclusion Vancomycin causes a variety of HSRs; the most commonly identified were nonimmediate HSRs, with LABD being most frequent. We observed a high frequency of HSR mortality. Further data are needed to understand the frequency and severity of vancomycin HSRs.

Background The prevalence of drug allergies documented in electronic health records (EHRs) of large patient populations is understudied. Objective We aimed to describe the prevalence of common drug allergies and patient characteristics documented in EHRs of a large healthcare network over the last two decades. Methods Drug allergy data were obtained from EHRs of patients who visited two large tertiary care hospitals in Boston from 1990 to 2013. The prevalence of each drug and drug class was calculated and compared by sex and race/ethnicity. The number of allergies per patient was calculated and the frequency of patients having 1, 2, 3…, or 10+ drug allergies was reported. We also conducted a trend analysis by comparing the proportion of each allergy to the total number of drug allergies over time. Results Among 1 766 328 patients, 35.5% of patients had at least one reported drug allergy with an average of 1.95 drug allergies per patient. The most commonly reported drug allergies in this population were to penicillins (12.8%), sulfonamide antibiotics (7.4%), opiates (6.8%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (3.5%). The relative proportion of allergies to angiotensin-converting enzyme (ACE) inhibitors and HMG CoA reductase inhibitors (statins) have more than doubled since early 2000s. Drug allergies were most prevalent among females and white patients except for NSAIDs, ACE inhibitors, and thiazide diuretics, which were more prevalent in black patients. Conclusion Females and white patients may be more likely to experience a reaction from common medications. An increase in reported allergies to ACE inhibitors and statins is noteworthy.

The penicillin allergy label has been consistently linked with deleterious effects that span the health care spectrum, including suboptimal clinical outcomes, the emergence of bacterial resistance, and increased health care expenditures. These risks have recently motivated professional organizations and public health institutes to advocate for the implementation of penicillin allergy delabeling initiatives; however, the burden of delabeling millions of patients is too expansive for any one discipline to bear alone. This review presents the unique perspectives and roles of various stakeholder groups involved in penicillin allergy diagnosis, assessment, and delabeling; we emphasize opportunities, barriers, and promising areas of innovation. We summarize penicillin allergy methods and tools that have proven successful in delabeling efforts. A multidisciplinary approach to delabeling patients with reported penicillin allergy, bolstered by evidence-based clinical practices, is recommended to reduce the risks that associate with the penicillin allergy label.

Background Serum immunoglobulin G (IgG) concentrations are integral to the workup of immune deficiencies and IgG4-related disease (IgG4-RD). Demographic differences in IgG concentrations are poorly described but can influence test interpretation, contribute to racial disparities in primary immunodeficiency diagnosis, and explain demographic differences in IgG concentrations in IgG4-RD. Objective To assess differences in IgG and IgG subclass concentrations according to sex and race. Methods We identified patients with IgG and IgG subclass concentrations measured in a large health care system. Multivariate-adjusted differences in IgG and IgG subclass concentrations and the proportion of subjects with results outside of reference ranges according to sex and race were estimated. Results Of the 12,851 patients, the mean age was 54.7 years and 7917 (62%) were female. Of these, 11,673 (91%) were white, 611 (5%) were black, and 302 (2%) were Asian. Compared with the mean concentrations of white patients, Asian and black patients had higher mean concentrations of IgG (1340.0 and 1504.4 vs 988.1 mg/dL, P Conclusion Immunoglobin G and IgG subclass concentrations differ according to sex and race. These findings may have implications for the interpretation of these test results but require confirmation in diverse, healthy populations.

Background The epidemiology of hospital adverse reactions (ARs), particularly allergic reactions, or hypersensitivity reactions (HSRs), is poorly defined. To determine priorities for allergy safety in healthcare, we identified and described safety reports of allergic reactions. Methods We searched the safety report database of a large academic medical center from April 2006 to March 2016 using 101 complete, truncated, and/or misspelled key words related to allergic symptoms, treatments, and culprits (e.g., medications, foods). Patient and event data were summarized for ARs and two types of ARs, HSRs and side effects/toxicities. Results Among 9111 key word search-identified events, 876 (10%) were ARs, of which 436 (5%) were HSRs and the remaining 440 (5%) were side effect reactions or toxicities. Whereas the most common HSRs were simple cutaneous reactions (83%), the following severe immediate HSRs were also identified: shortness of breath (16%), anaphylaxis (14%), and angioedema (12%). Most HSRs were caused by drugs (81%), with antibiotics (26%), particularly β-lactams (11%), and vancomycin (8%), commonly implicated. Other causes of drug HSRs included contrast agents (24%), chemotherapeutics (7%), and opioids (6%). Nondrug HSRs were from blood products (8%), latex (3%), and devices (3%). Food reactions were rarely identified (1%). Conclusions We identified ARs, HSRs, and side effects/toxicities, contained in a decade of safety reports at an academic medical center. Allergy safety in the healthcare setting should target approaches to common and severe reactions, with a focus on the safe administration of β-lactams, vancomycin, contrast agents, chemotherapeutics, and opioids. Priority nondrug HSR culprits include blood products, latex, and devices.

β-Lactam antibiotics are among the safest and most effective antibiotics. Many patients report allergies to these drugs that limit their use, resulting in the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance and adverse events.Approximately 10% of the US population has reported allergies to the β-lactam agent penicillin, with higher rates reported by older and hospitalized patients. Although many patients report that they are allergic to penicillin, clinically significant IgE-mediated or T lymphocyte-mediated penicillin hypersensitivity is uncommon (5%). Currently, the rate of IgE-mediated penicillin allergies is decreasing, potentially due to a decreased use of parenteral penicillins, and because severe anaphylactic reactions to oral amoxicillin are rare. IgE-mediated penicillin allergy wanes over time, with 80% of patients becoming tolerant after a decade. Cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, less than the 8% reported previously. Some patients have a medical history that suggests they are at a low risk for developing an allergic reaction to penicillin. Low-risk histories include patients having isolated nonallergic symptoms, such as gastrointestinal symptoms, or patients solely with a family history of a penicillin allergy, symptoms of pruritus without rash, or remote (10 years) unknown reactions without features suggestive of an IgE-mediated reaction. A moderate-risk history includes urticaria or other pruritic rashes and reactions with features of IgE-mediated reactions. A high-risk history includes patients who have had anaphylaxis, positive penicillin skin testing, recurrent penicillin reactions, or hypersensitivities to multiple β-lactam antibiotics. The goals of antimicrobial stewardship are undermined when reported allergy to penicillin leads to the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance, including increased risk of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Broad-spectrum antimicrobial agents also increase the risk of developing Clostridium difficile (also known as Clostridioides difficile) infection. Direct amoxicillin challenge is appropriate for patients with low-risk allergy histories. Moderate-risk patients can be evaluated with penicillin skin testing, which carries a negative predictive value that exceeds 95% and approaches 100% when combined with amoxicillin challenge. Clinicians performing penicillin allergy evaluation need to identify what methods are supported by their available resources.Many patients report they are allergic to penicillin but few have clinically significant reactions. Evaluation of penicillin allergy before deciding not to use penicillin or other β-lactam antibiotics is an important tool for antimicrobial stewardship.

OBJECTIVES: To examine associations of race/ethnicity and purported risk factors with hospitalized allopurinol-associated severe cutaneous adverse reactions (AASCARs). METHODS: We used US Medicaid data to identify incident allopurinol users between 1999 and 2012. We examined the risk of hospitalized AASCARs according to race/ethnicity and purported key risk factors and calculated relative risks (RR). RESULTS: Among 400,401 allopurinol initiators, we documented 203 hospitalized AASCAR cases (1 in 1,972 initiators). The average AASCAR hospitalization was 9.6 days and 43 individuals (21%) died. The multivariable-adjusted RRs for AASCARs among Blacks, Asians, and Native Hawaiians/Pacific Islanders compared with Whites or Hispanics were 3.00 (95% confidence interval [CI], 2.18 to 4.14), 3.03 (95% CI, 1.72 to 5.34), and 6.68 (95% CI, 4.37 to 10.22), respectively. Female sex, older age (≥60 years), chronic kidney disease (CKD), and initial allopurinol dose (>100 mg/day) were independently associated with a 2.5-, 1.7-, 2.3-, and 1.9-fold higher risk of AASCAR, respectively. In our combined demographic analysis, older women (≥60 years) of a high-risk race/ethnicity (Blacks, Asians, or Native Hawaiians/Pacific Islanders) had over a 12-fold higher risk of hospitalized AASCARs than younger men of a low-risk race/ethnicity (Whites or Hispanics) (multivariable-adjusted RR, 12.25; 95% CI, 6.46 to 23.25). CONCLUSIONS: This racially-diverse (yet mostly White) cohort study indicates that the risk of hospitalized AASCAR is rare overall, although Blacks, Asians, and Native-Hawaiians/Pacific-Islanders have a substantially higher risk of hospitalized AASCARs, particularly among older women. These data also support the practice of initiating allopurinol at a low dose (e.g., ≤100 mg/day).

The cost of adverse drug reactions (ADRs) in the United States exceeds $4.2 billion annually. ADRs comprise 3–6% of all hospital admissions and complicate 10–15% of existing hospitalizations. Drug hypersensitivity reactions (HSRs) represent about 20% of ADRs and include anaphylaxis, angioedema, and cutaneous reactions that range from a mild drug rash to severe cutaneous adverse reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis. HSR cost is determined by the resources required to diagnose and treat the patient's reaction. Ultimately, the type of medical visit required for HSR evaluation and treatment establishes much of the cost, with a simple doctor’s visit being less costly than an emergency department visit or hospitalization. HSR chronicity additionally impacts cost; therefore, acute urticaria from a nonsteroidal antiinflammatory drug is less costly than a chemotherapy-induced delayed relapsing and remitting toxic dermatitis. Unverified drug allergies result in costlier care and a large economic impact. The most common misreported allergy is penicillin allergy, which increases costs through the use of costlier alternative antibiotics and/or longer hospitalizations, which result from treatment failures, the development of drug-resistant organisms, or healthcare-associated infections. To date, there have been few cost-effectiveness analyses in drug allergy, with most focusing on specific class I major histocompatibility complex molecules, including abacavir and HLA-B∗57:01, carbamazepine and HLA-B∗15:02, and allopurinol and HLAB∗58:01 and HLA-A∗31:01. Further economic analyses and cost-effective analyses related to drug allergy may help improve clinical outcomes and reduce healthcare costs.

BACKGROUND: Although drugs represent a common cause of anaphylaxis, few large studies of drug-induced anaphylaxis have been performed.OBJECTIVE: To describe the epidemiology and validity of reported drug-induced anaphylaxis in the electronic health records (EHRs) of a large United States healthcare system.METHODS: Using EHR drug allergy data from 1995-2013, we determined the population prevalence of anaphylaxis including anaphylaxis prevalences over time, and the most commonly implicated drugs/drug classes reported to cause anaphylaxis. Patient risk factors for drug-induced anaphylaxis were assessed using a logistic regression model. Serum tryptase and allergist visits were used to assess the validity and follow up of EHR-reported anaphylaxis.RESULTS: Among 1,756,481 patients, 19,836 (1.1%) reported drug-induced anaphylaxis: Penicillins (45.9 per 10,000), sulfonamide antibiotics (15.1 per 10,000), and nonsteroidal anti-inflammatory drugs (NSAIDs) (13.0 per 10,000) were most commonly implicated. Patients with white race (odds ratio [OR] 2.38, 95% CI 2.27-2.49), female sex (OR 2.20, 95% CI 2.13-2.28), systemic mastocytosis (OR 4.60, 95% CI 2.66-7.94), Sjögren's syndrome (OR 1.94, 95% CI 1.47-2.56), and asthma (OR 1.50, 95% CI 1.43-1.59) had an increased odds of drug-induced anaphylaxis. Serum tryptase was performed in 135 (CONCLUSION: EHR-reported anaphylaxis occurred in approximately 1% of patients, most commonly from penicillins, sulfonamide antibiotics, and NSAIDs. Females, whites, and patients with mastocytosis, Sjögren's syndrome, and asthma had increased odds of reporting drug-induced anaphylaxis. The low observed frequency of tryptase testing and specialist evaluation emphasize the importance of educating providers on anaphylaxis management.

Background A reported penicillin allergy may compromise receipt of recommended antibiotic prophylaxis intended to prevent surgical site infections (SSIs). Most patients with a reported penicillin allergy are not allergic. We determined the impact of a reported penicillin allergy on the development of SSIs. Methods In this retrospective cohort study of Massachusetts General Hospital hip arthroplasty, knee arthroplasty, hysterectomy, colon surgery, and coronary artery bypass grafting patients from 2010 to 2014, we compared patients with and without a reported penicillin allergy. The primary outcome was an SSI, as defined by the Centers for Disease Control and Prevention's National Healthcare Safety Network. The secondary outcome was perioperative antibiotic use. Results Of 8385 patients who underwent 9004 procedures, 922 (11%) reported a penicillin allergy, and 241 (2.7%) had an SSI. In multivariable logistic regression, patients reporting a penicillin allergy had increased odds (adjusted odds ratio, 1.51; 95% confidence interval, 1.02-2.22) of SSI. Penicillin allergy reporters were administered less cefazolin (12% vs 92%; P < .001) and more clindamycin (49% vs 3%; P < .001), vancomycin (35% vs 3%; P < .001), and gentamicin (24% vs 3%; P < .001) compared with those without a reported penicillin allergy. The increased SSI risk was entirely mediated by the patients' receipt of an alternative perioperative antibiotic; between 112 and 124 patients with reported penicillin allergy would need allergy evaluation to prevent 1 SSI. Conclusions Patients with a reported penicillin allergy had a 50% increased odds of SSI, attributable to the receipt of second-line perioperative antibiotics. Clarification of penicillin allergies as part of routine preoperative care may decrease SSI risk.