Development of a machine learning algorithm based on administrative claims data for identification of ED anaphylaxis patient visits.

Background: Epidemiologic studies of anaphylaxis commonly rely on International Classification of Diseases (ICD) codes to identify anaphylaxis cases, which may lead to suboptimal epidemiologic classification. Objective: We sought to develop and assess the accuracy of a machine learning algorithm using ICD codes and other administrative data compared with ICD code-only algorithms to identify emergency department (ED) anaphylaxis visits. Methods: We conducted a retrospective review of ED visits from January 2013 to September 2017. Potential ED anaphylaxis visits were identified using 3 methods: anaphylaxis ICD diagnostic codes (method 1), ICD symptom-based codes with or without a code indicating an allergic trigger (method 2), and ICD codes indicating a potential allergic reaction only (method 3). A machine learning algorithm was developed from administrative data, and test characteristics were compared with ICD code-only algorithms. Results: A total of 699 of 2191 (31.9%) potential ED anaphylaxis visits were classified as anaphylaxis. The sensitivity and specificity of method 1 were 49.1% and 87.5%, respectively. Method 1 used in combination with method 2 resulted in a sensitivity of 53.9% and a specificity of 68.7%. Method 1 used in combination with method 3 resulted in a sensitivity of 98.4% and a specificity of 15.1%. The sensitivity and specificity of the machine learning algorithm were 87.3% and 79.1%, respectively. Conclusions: ICD coding alone demonstrated poor sensitivity in identifying cases of anaphylaxis, with venom-related anaphylaxis missing 96% of cases. The machine learning algorithm resulted in a better balance of sensitivity and specificity and improves upon previous strategies to identify ED anaphylaxis visits.

Risks and safety of biologics: A practical guide for allergists.

Biologic agents are a rapidly expanding class of medications, and several options are now available for the management of allergic and immunologic disorders. The risks of biologic therapy need to be understood in order to adequately counsel patients and appropriately monitor for potential adverse events. We sought to provide a comprehensive review of the risks and adverse effects reported for the current FDA-approved biologics used in management of allergic and immunologic disorders, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, tezepelumab and tralokinumab. Our review focuses on the risk of hypersensitivity reactions, pregnancy-specific considerations, risk of infection and risk of malignancy. We also highlight drug-specific adverse events and unique safety issues identified in case reports.

Current and emerging biologic therapies targeting eosinophilic disorders.

Eosinophilic disorders include a wide array of conditions in which eosinophils play a primary pathophysiologic role. While historically treated with corticosteroids and immunosuppressants, knowledge of eosinophil biology has led to the development of several biologics targeting eosinophils. In this review, we discuss the current US Food and Drug Administration (FDA) approved eosinophil-specific biologics targeting IL-5 (mepolizumab and reslizumab) and IL-5R (benralizumab) along with biologics under investigation targeting siglec-8 (lirentelimab). We discuss efficacy and safety data from trials of these medications in conditions including eosinophilic asthma, hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), and eosinophilic gastrointestinal disease (EGID). Additionally, we discuss case reports utilizing these medications in conditions including drug reaction with eosinophilia and systemic symptoms (DRESS), allergic bronchopulmonary aspergillosis (ABPA), and eosinophilic pneumonia, among others. While eosinophilic targeting biologic therapy has been successful in eosinophilic asthma, HES, EGPA, and CRSwNP leading to FDA approval for these conditions, trials treating EoE and EGID have been disappointing to date. Given the increasing number of trials utilizing these biologics, it will be imperative for the allergist-immunologist to stay up to date on the latest treatment options to provide the most optimal care for eosinophilic disorders.

Elevating Health Disparities Education Among Trainees and Physicians.

Health disparities disproportionately affect patients in racial and ethnic minority groups, and these disparities are linked to economic, environmental, and social disadvantage. It is widely known that health disparities impact patients with allergic and immunologic conditions, yet universal and comprehensive training in health disparities is lacking. More robust educational opportunities are needed to fully equip trainees with tools to recognize and develop effective strategies to reduce the burden of health disparities. Also, there are no universal standards or requirements for professional medical boards in their respective maintenance of certification programs that will ensure ongoing training for practicing providers that will help them identify and manage individual or societal issues such as social determinants that contribute to health disparities. Further, the long-term impact of systematic discrimination, implicit and overt bias, and medical mistrust among populations most often affected by disparities compounds the complexity of the methods and types of training that is desperately needed to overcome health disparities. We provide a commentary on important topics that should be addressed during allergy and immunology training and beyond. We further highlight strategies and tools that should be used to tackle this important issue affecting millions of patients under our specialty care. It is past time for us to go beyond the bedside and comprehensively integrate health disparities training in our fellowship programs and in our practices.

Anaphylaxis: Epidemiology and Differential Diagnosis.

Anaphylaxis-related emergency department (ED) visits and hospitalizations are increasing. Triggers for anaphylaxis include food, medications, and stinging insects. Idiopathic anaphylaxis accounts for 30% to 60% of cases of anaphylaxis in adults and up to 10% of cases in children with novel allergens such as galactose-α-1,3 galactose reclassifying these cases. Recent practice guidelines have recommended against the routine use of systemic corticosteroids and antihistamines for the prevention of biphasic reactions and recommend an extended observation, up to 6 hours, for those with risk factors for biphasic anaphylaxis and those with lack of access to epinephrine and to emergency medical services.

Patients Taking ß-Blockers Do Not Require Increased Doses of Epinephrine for Anaphylaxis.

BACKGROUND: ß-Blocker use has been associated with increased anaphylaxis severity. OBJECTIVE: We aimed to assess for an association between ß-blocker use and requirement for more than 1 dose of epinephrine for anaphylaxis management. METHODS: We conducted a retrospective observational study of patients seen in our emergency department for anaphylaxis between April 2008 and January 2015. The primary outcome measure was the number of doses of epinephrine. Associations with repeat epinephrine administration (>1 vs ≤1 dose of epinephrine) and associations with any epinephrine administration (>0 vs 0 dose) were evaluated using logistic regression models and summarized as odds ratio (OR) and 95% CIs. The study was powered to detect a 10% or greater difference in need for repeat epinephrine administration between patients who were and were not taking ß-blocker medications. RESULTS: Of 789 patient visits with a documented medication history included in the study, 63 (8%) required more than 1 epinephrine dose and 83 (11%) were on ß-blocker therapy. Among patients who required more than 1 epinephrine dose, 8 (13%) were taking a ß-blocker, compared with 75 patients (10%) who received 0 or 1 dose of epinephrine (OR, 1.26; 95% CI, 0.58-2.75). Among patients who required at least 1 epinephrine dose, 41 (9%) were taking a ß-blocker, compared with 42 patients (12%) who received no epinephrine (OR, 0.73; 95% CI, 0.46-1.14). CONCLUSIONS: ß-Blocker use may not be clinically significant with regard to the need for epinephrine dosing among emergency department patients with anaphylaxis.

Evaluation and Management of Penicillin Allergy.

Penicillin allergy is the most commonly reported drug allergy in the United States. Although penicillin allergy is widely reported, 80% to 90% of individuals with self-reported penicillin allergy are actually able to tolerate penicillins after undergoing evaluation for penicillin allergy. Because most patients with self-reported penicillin allergy will have subsequent negative allergy testing results and tolerate penicillins, they may be unnecessarily exposed to broader-spectrum antibiotics. Use of such antibiotics leads to increased risks of developing antibiotic-resistant microorganisms and incur higher health care utilization costs. In this article, we provide an overview of penicillin allergy and its clinical manifestations as well as an approach for the evaluation and management of penicillin allergy.

Outcomes of Emergency Department Anaphylaxis Visits from 2005 to 2014.

BACKGROUND: Although the incidence of anaphylaxis appears to be increasing, trends in anaphylaxis-related health care utilization are not well understood. OBJECTIVE: To better understand the potential increasing health care burden, we analyzed the changes in anaphylaxis-related health care utilization, including emergency department (ED) discharges, observation stays, inpatient admissions, intensive care unit admissions, and endotracheal intubations. METHODS: We conducted an observational study examining outcomes of anaphylaxis-related ED visits between January 1, 2005, and December 31, 2014. We analyzed administrative claims data from OptumLabs Data Warehouse, which includes more than 100 million Medicare Advantage and privately insured enrollees in the United States. We studied trends in the proportions of ED-related anaphylaxis visits based on demographic characteristics, triggers, and ED disposition for our study population. RESULTS: Among 56,212 anaphylaxis-related ED visits during a 10-year period, the proportion of patient observation/inpatient admissions increased by 37.6% (P = .02), from 13.2% of anaphylaxis-related ED visits in 2005 to 18.2% in 2014. The proportion of patients admitted to the intensive care unit increased by 27.4% (P = .001), from 4.5% in 2005 to 5.8% in 2014. Proportions of endotracheal intubation increased by 145.2% (P < .001). CONCLUSIONS: The increasing proportions of observation/inpatient admissions, intensive care unit admissions, and endotracheal intubations suggest an increase in anaphylaxis severity. Enhanced awareness of these trends among patients, practitioners, and the community is necessary to create effective strategies to prevent anaphylaxis and decrease associated adverse consequences.

Sublingual Immunotherapy Dosing Regimens: What Is Ideal?

Sublingual immunotherapy (SLIT) is a treatment for allergic respiratory diseases that has demonstrated efficacy and safety. Several formulations of SLIT are now available worldwide for treatment of allergic rhinitis (AR). Grass tablets containing 15 to 25 µg of group 5 major allergen reduced combined AR symptoms and medication use by 23% to 41% in 3 treatment years and 2 follow-up years. Ragweed pollen tablets (12 µg of Ambrosia artemisiifolia 1) and liquid extracts (50 µg of Ambrosia artemisiifolia 1) reduced combined AR symptoms and medication use by 26% and 43%, respectively. House dust mite tablets containing 300 index of reactivity (16 µg of Dermatophagoides pteronyssinus 1 and 68 µg of Dermatophagoides farinae 1) reduced AR symptoms by 17.9% and 17.0% in 1 treatment year and 1 follow-up year, respectively. A different house dust mite tablet (12 standardized quality house dust mite) was able to reduce the risk of asthma exacerbation compared with placebo (hazard ratio, 0.69; 95% CI, 0.50-0.96). Most adverse events were local and mild to moderate in severity. For SLIT products reviewed herein, effective doses range from 1.12 to 84 µg of major allergen(s). However, allergen content is not uniformly standardized, can be expressed in arbitrary or proprietary units (depending on the manufacturer), and assays for determination of allergen content are highly variable. Thus, results from one study of a given product cannot be extrapolated to other products. Despite these limitations, this Clinical Management Review aims to provide practitioners with relevant information on the dosing of selected SLIT formulations in the treatment of allergic respiratory disease.

International Consensus (ICON): allergic reactions to vaccines.

BACKGROUND: Routine immunization, one of the most effective public health interventions, has effectively reduced death and morbidity due to a variety of infectious diseases. However, allergic reactions to vaccines occur very rarely and can be life threatening. Given the large numbers of vaccines administered worldwide, there is a need for an international consensus regarding the evaluation and management of allergic reactions to vaccines. METHODS: Following a review of the literature, and with the active participation of representatives from the World Allergy Organization (WAO), the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the American College of Allergy, Asthma, and Immunology (ACAAI), the final committee was formed with the purpose of having members who represented a wide-range of countries, had previously worked on vaccine safety, and included both allergist/immunologists as well as vaccinologists. RESULTS: Consensus was reached on a variety of topics, including: definition of immediate allergic reactions, including anaphylaxis, approaches to distinguish association from causality, approaches to patients with a history of an allergic reaction to a previous vaccine, and approaches to patients with a history of an allergic reaction to components of vaccines. CONCLUSIONS: This document provides comprehensive and internationally accepted guidelines and access to on-line documents to help practitioners around the world identify allergic reactions following immunization. It also provides a framework for the evaluation and further management of patients who present either following an allergic reaction to a vaccine or with a history of allergy to a component of vaccines.

Prospective Validation of the NIAID/FAAN Criteria for Emergency Department Diagnosis of Anaphylaxis.

BACKGROUND: Anaphylaxis diagnostic criteria were proposed at the Second Symposium on the Definition and Management of Anaphylaxis. These criteria were 97% sensitive and 82% specific when retrospectively validated. OBJECTIVE: To prospectively evaluate the diagnostic accuracy of the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria for diagnosis of anaphylaxis in the emergency department (ED). METHODS: We conducted a prospective observational study of patients seen in our institution's ED from April 2010 to March 2013. Patients seeking care for an allergic reaction and possible anaphylaxis were enrolled. Patients and providers completed questionnaires regarding onset, trigger, and signs and symptoms. Records were reviewed independently and blindly by 2 board-certified allergist-immunologists, and their final diagnosis (anaphylaxis vs no anaphylaxis) was used as the reference standard. Two-by-two tables were built, and test characteristics were calculated. RESULTS: Among the 174 enrolled patients, 91 (52%) met the NIAID/FAAN criteria for anaphylaxis. The allergist-immunologists diagnosed 61 cases of anaphylaxis (35%), of which 58 (95%) also satisfied the NIAID/FAAN criteria. The interrater agreement between allergist-immunologists was substantial (κ = 0.7). Test characteristics (95% CIs) of the NIAID/FAAN criteria were as follows: sensitivity, 95.1% (85.4%-98.7%); specificity, 70.8% (61.4%-78.8%); positive predictive value, 63.7% (52.9%-73.4%); negative predictive value, 96.4% (89.1%-99.1%); positive likelihood ratio, 3.26; and negative likelihood ratio, 0.07. CONCLUSIONS: Prospectively, the NIAID/FAAN criteria continued to be highly sensitive (95%) but had lower specificity (71%) than on retrospective assessment. These criteria are likely to be useful for the diagnosis of anaphylaxis in the ED.

Appropriateness of epinephrine use in ED patients with anaphylaxis.

BACKGROUND: Studies have demonstrated low rates of emergency department (ED) epinephrine administration for anaphylaxis patients, suggestive of ED undertreatment of anaphylaxis. Our study assessed the appropriateness of ED epinephrine administration in anaphylaxis management. METHODS: A prospective observational study was conducted involving ED patients presenting with possible allergic reactions. Patients and ED providers completed questionnaires regarding the suspected trigger, signs and symptoms, and prehospital treatment. Two board-certified allergists-immunologists independently reviewed the questionnaires, as well as electronic health records, to determine whether the cases represented anaphylaxis and whether ED epinephrine administration was appropriate. RESULTS: Among 174 patients enrolled in the study, 61 (35%) were confirmed to have anaphylaxis. Overall, 47 anaphylaxis patients (77%) received epinephrine either before ED arrival or in the ED. In the latter situation, 24 anaphylaxis patients (39%) received epinephrine and 37 (61%) did not. Of the patients who received ED epinephrine, the allergists-immunologists determined that its administration was appropriate in all cases (95% confidence interval [CI], 83%-100%). Among the 37 patients who did not receive ED epinephrine, the allergists-immunologists determined that nonadministration of epinephrine was appropriate in 36 patients (97%; 95% CI, 84%-100%). The allergists-immunologists determined that overall, ED management was appropriate for 60 (98%) of 61 patients with anaphylaxis (95% CI, 90%-100%). CONCLUSIONS: Although more than 60% of anaphylaxis patients did not receive epinephrine in the ED, the allergists-immunologists deemed ED management appropriate in 98% of total cases. Previous retrospective studies may underestimate the appropriateness of ED anaphylaxis management, particularly when prehospital epinephrine administration is not reported.