Drug-induced Anaphylaxis Research Articles

Management of Patients During Acute Reaction Induced by Drugs

Anaphylaxis is the most severe form of an allergic reaction and is characterized by being rapid in onset with potentially life-threatening airway, breathing, or circulatory problems; medications are able to provoke immediate acute reactions whose severity varies from mild (i.e., urticaria) to severe reactions (anaphylaxis). The management and prevention of anaphylactic reactions represent a crucial challenge for allergists that must perfectly know the symptoms and the best treatments of this severe disease. Acute treatment of anaphylaxis is based on the immediate administration of adrenaline, which represents the drug of choice and should be given immediately to any patient with suspected anaphylaxis. In case of drug-induced anaphylaxis, the allergological work up includes skin tests, in vitro tests, and drug challenges. Desensitization safely permits the administration of the needed medication and provides a temporary tolerance to the drugs that patients have presented immediate reactions to, including anaphylaxis and delayed reactions non-SCARS (severe cutaneous adverse drug reactions). First of all, this review focuses on the best treatment of anaphylaxis provoked by drugs and underlines the allergological work up of the patients. In the second part, special conditions, such as anaphylaxis during chemotherapy or radio contrast media (RCM) administration or in patients with mastocytosis, are analyzed.

Are drugs more dangerous?: Drug-induced anaphylaxis across the world

Drug-induced anaphylaxis (DIA) is a well-recognized risk factor for virtually all classes of medications. The incidence and specific risk factors vary widely depending on the class of drug and reported populations. This perspective addresses recent data reported on DIA and its impact on the understanding of the epidemiology, pathophysiology, and management of anaphylaxis.

Refractory Anaphylaxis: Data From the European Anaphylaxis Registry.

Refractory anaphylaxis (unresponsive to treatment with at least two doses of minimum 300 μg adrenaline) is a rare and often fatal hypersensitivity reaction. Comprehensive data on its definition, prevalence, and risk factors are missing. Using the data from the European Anaphylaxis Registry (11,596 cases in total) we identified refractory anaphylaxis cases (n = 42) and analyzed these in comparison to a control group of severe anaphylaxis cases (n = 4,820). The data show that drugs more frequently elicited refractory anaphylaxis (50% of cases, p < 0.0001) compared to other severe anaphylaxis cases (19.7%). Cases elicited by insects (n = 8) were more often due to bees than wasps in refractory cases (62.5 vs. 19.4%, p = 0.009). The refractory cases occurred mostly in a perioperative setting (45.2 vs. 9.05, p < 0.0001). Intramuscular adrenaline (as a first line therapy) was administered in 16.7% of refractory cases, whereas in 83.3% of cases it was applied intravenously (significantly more often than in severe anaphylaxis cases: 12.3%, p < 0.0001). Second line treatment options (e.g., vasopression with dopamine, methylene blue, glucagon) were not used at all for the treatment of refractory cases. The mortality rate in refractory anaphylaxis was significantly higher (26.2%) than in severe cases (0.353%, p < 0.0001). Refractory anaphylaxis is associated with drug-induced anaphylaxis in particular if allergens are given intravenously. Although physicians frequently use adrenaline in cases of perioperative anaphylaxis, not all patients are responding to treatment. Whether a delay in recognition of anaphylaxis is responsible for the refractory case or whether these cases are due to an overflow with mast cell activating substances—requires further studies. Reasons for the low use of second-line medication (i.e., methylene blue or dopamine) in refractory cases are unknown, but their use might improve the outcome of severe refractory anaphylaxis cases.

Drug-induced anaphylaxis—elicitors, mechanisms and diagnosis

Abstract Drugs are one of the major causes of anaphylaxis. For example 2346 cases of drug-induced anaphylaxis were reported to the anaphylaxis register as of March 2019. The most common triggers of drug-induced anaphylaxis were nonsteroidal anti-inflammatory drugs (NSAIDs; n = 902) and antibiotics (n = 721). Drug-induced anaphylaxis can be caused by IgE-dependent (e.g., penicillins) and IgE-independent mechanisms. Recently MRG-PX2 has been identified as a receptor for non-IgE-dependent mechanisms. Drug-induced anaphylaxis results more frequently in lethal reactions and is more commonly associated with cardiovascular symptoms. Also therapy refractory anaphylaxis is more frequently triggered by drugs. For the diagnosis of drug-induced anaphylaxis current national and international guidelines should be followed including provocation tests to avoid future reactions.

Drug-induced anaphylaxis, elicitors, risk factors, and management in Latin America

Drug-induced anaphylaxis, elicitors, risk factors, and management in Latin America

The mast cell receptor MrgX2 and drug-induced anaphylaxis

The mast cell receptor MrgX2 and drug-induced anaphylaxis

Medical and pathologic characteristics of fatal anaphylaxis: a Spanish nationwide 17-year series.

Forensic series on fatal anaphylaxis are scarce, probably because the diagnosis of anaphylaxis is often complex and the incidence is low. We report on the medicolegal, demographic and histopathological characteristics of a series of sudden deaths which were investigated for anaphylaxis at the Spanish National Institute of Toxicology and Forensic Sciences (INTCF) over a 17-year period (1998-2015). A total of 122 undetermined sudden deaths from a high percentage of Spanish regions (81.5% of the total population) were sent to the INTCF with anaphylaxis as the suspected cause of death for histological, biochemical, and medicolegal investigation. Two certified allergists confirmed that 46 of the 122 cases were fatal anaphylaxis. The results indicated a median age of 51years (IQR = 29) and a male predominance (76%). The main causes of anaphylaxis were drugs (41%), hymenoptera stings (33%), and food (13%). A previous allergic event had been reported in both food anaphylaxis (67%) and drug anaphylaxis (53%). The deaths occurred in health care settings (37%), at home (22%), and outside the home (26.09%). Histopathology data were available for 40 individuals. The most frequent autopsy findings were angioedema of the upper airways (50%), pulmonary edema (47.5%), atheromatosis of coronary vessels (32.5%), and pulmonary congestion (27.5%). Our findings for fatal anaphylaxis indicated a predominance of men, older age (≥50years) and death in a health care setting (one-third of cases). Previous episodes had occurred in two-thirds of cases of food-induced anaphylaxis and in half of the cases of drug-induced anaphylaxis.

An IgG-induced neutrophil activation pathway contributes to human drug-induced anaphylaxis.

Anaphylaxis is a systemic acute hypersensitivity reaction that is considered to depend on allergen-specific immunoglobulin E (IgE) antibodies and histamine release by mast cells and basophils. Nevertheless, allergen-specific IgG antibodies have been proposed to contribute when the allergen is an abundant circulating large molecule, e.g., after infusions of therapeutic antibodies or dextran. Data from animal models demonstrate a pathway involving platelet-activating factor (PAF) release by monocytes/macrophages and neutrophils activated via their Fc gamma receptors (FcγRs). We hypothesized that such a pathway may also apply to small drugs and could be responsible for non-IgE-mediated anaphylaxis and influence anaphylaxis severity in humans. We prospectively conducted a multicentric study of 86 patients with suspected anaphylaxis to neuromuscular-blocking agents (NMBAs) during general anesthesia and 86 matched controls. We found that concentrations of anti-NMBA IgG and markers of FcγR activation, PAF release, and neutrophil activation correlated with anaphylaxis severity. Neutrophils underwent degranulation and NETosis early after anaphylaxis onset, and plasma-purified anti-NMBA IgG triggered neutrophil activation ex vivo in the presence of NMBA. Neutrophil activation could also be observed in patients lacking evidence of classical IgE-dependent anaphylaxis. This study supports the existence of an IgG-neutrophil pathway in human NMBA-induced anaphylaxis, which may aggravate anaphylaxis in combination with the IgE pathway or underlie anaphylaxis in the absence of specific IgE. These results reconcile clinical and experimental data on the role of antibody classes in anaphylaxis and could inform diagnostic approaches to NMBA-induced acute hypersensitivity reactions.

Drug-Induced Anaphylaxis in Children

To describe and analyze epidemiology, major triggers, diagnosis, and management of drug-induced anaphylaxis in pediatric population. Despite the fact that foods are the most common elicitors of anaphylaxis during childhood, frequency of those reactions during adolescence seems to be increasing and they are associated with more severe reactions. Betactam antibiotics and non-steroidal anti-inflammatory drugs are described as major triggers of those reactions. Despite its higher severity, anaphylaxis continues to be underrecognized and undertreated. Drugs are associated with more severe anaphylactic reactions in all age groups, but it is still underdiagnosed and wrongly managed. Patients who seek assistance for anaphylaxis in the emergency departments should be referred to an allergist consultation and pediatricians should be better trained to recognize and correctly manage this severe condition.

Medical malpractice related to drug-induced anaphylaxis: An analysis of lawsuit judgments in South Korea.

Drug-induced anaphylaxis (DIA) is a highly paradoxical disorder involving a fatal response to medicines prescribed for therapeutic purposes. This study aimed to improve the awareness on DIA and to prevent errors through an analysis of lawsuit judgments.Sentenced judgments involving DIA from 1998 to 2017 using the database of the Korean Supreme Court Judgment System were collected. General characteristics, results, and recognized negligence of DIA litigation cases were analyzed.Of 27 lawsuit cases included, antibiotics (n = 6, 22.2%), radiocontrast media (n = 6, 22.2%), and non-steroidal anti-inflammatory drugs (n = 5, 18.5%) were the most common drugs that had caused DIA. Cardiac arrest was reported in 23 cases (85.2%). The median time interval from drug administration to diagnosis and from diagnosis to cardiac arrest were 7 (interquartile range, IQR = 0–35) and 5 minutes (IQR = 0–33), respectively, suggesting insufficient time to cope with anaphylaxis. Consequently, either death (n = 18, 66.7%) or ischemic brain injury (n = 9, 33.3%) occurred in all cases. Violation of duty of care was recognized in 19 cases (70.4%) with median awarded amount of $106,060 (IQR = $70,296–$168,363). The recognized negligence included inadequate observation after drug administration (n = 6), delayed or missed epinephrine administration (n = 6), ignoring a history of allergy or drug hypersensitivity (n = 6), and prescription error (n = 5).It is necessary to improve the awareness on DIA, because making a trivial error in any process of history taking, drug prescription and administration, observation, and/or emergency treatment may have fatal consequences that can lead to indemnity.

Diagnosis and management of drug-induced anaphylaxis in children: An EAACI position paper.

Drug hypersensitivity reactions (DHR) constitute a major and common public health problem, particularly in children. One of the most severe manifestations of DHR is anaphylaxis, which might be associated with a life-threatening risk. During those past decades, anaphylaxis has received particularly a lot of attention and international consensus guidelines have been recently published. Whilst drug-induced anaphylaxis is more commonly reported in adulthood, less is known about the role of drugs in pediatric anaphylaxis. Betalactam antibiotics and non-steroidal anti-inflammatory drugs are the most commonly involved drugs, probably related to high prescription rates. Diagnosis relies on the recognition of symptoms pattern and is based on complete allergic workup, particularly including skin tests and/or specific IgE. However, the real diagnostic value of those tests to diagnose immediate reactions in children remains not well defined for a significant number of the drugs. Generally, a drug provocation test is discussed to confirm or exclude an immediate-onset drug-induced hypersensitivity. Although avoidance of the incriminated drug (and related drug) is the rule, rapid desensitization is useful in selected subgroups of patients. There is a need for large, multicentric studies, to evaluate the real diagnostic value of the currently available skin tests. Moreover there is also a need to develop new diagnostic tests in the future to improve the management of these children.

Incidence, etiology, predictors and outcomes of suspected drug hypersensitivity reactions in atertiary care university hospital's emergency department : Aretrospective study.

Allergic drug reactions are adverse drug reactions that result from aspecific immunologic response to amedication. Considering the epidemiological and clinical importance of drug allergy, this retrospective analysis focused on drug hypersensitivity in atertiary care university hospital emergency department (ED). In this study 74,929 ED records obtained from March 2012 to March 2015 were reviewed to determine the incidence, etiology, predictors and clinical features of drug hypersensitivity. The observed incidence of drug hypersensitivity was 0.87% of all ED admissions. It was significantly higher in female patients aged 18-29 years (2.26%; P < 0.0001) and during winter months (1.09%; P = 0.0058). Most patients had mild to moderate symptoms which regressed following ED treatment. Only five patients (7 per 100,000 ED visits) were diagnosed with drug-induced anaphylaxis, and only five patients were provisionally diagnosed with severe non-immediate reactions with systemic involvement. No patient died of drug hypersensitivity in the ED, and only asmall proportion required subsequent hospitalization. The most common causes of drug hypersensitivity reactions were amoxicillin and paracetamol. Drug hypersensitivity is acommon reason for tertiary centre emergency admissions. This is the largest analysis of ED drug hypersensitivity admissions so far. Beta-lactams were identified as the leading cause of drug hypersensitivity requiring ED evaluation, which also explains the peak of drug hypersensitivity cases during winter months when the use of these medications is highest.

Drug-Induced Anaphylaxis in a Vietnamese Pharmacovigilance Database: Trends and Specific Signals from a Disproportionality Analysis.

Despite the numerous studies investigating drug-induced anaphylaxis (DIA), understanding and quantitative data analysis in developing countries remain limited. The aim of our study is to describe and quantify DIA using the National Pharmacovigilance Database of Vietnam (NPDV). Spontaneous reporting of adverse drug reactions (ADRs) recorded between 2010 and 2016 were retrospectively analysed to identify DIA reports. The trend and characteristics of DIA cases were described. Multivariate disproportionality analysis was used for signal generation. Overall, 4873 DIA cases (13.2% of total ADRs) were recorded in the NPDV, 111 of which resulted in death (82% of total ADR-induced deaths) over a 7-year period. There was a remarkable increase in DIA reporting over time (p<0.001). The incidence rates of DIA reporting per total ADRs and per 100,000 inhabitants remained high (mean rates [95% CI] of 12.06 [9.88-14.24] and 0.77 [0.33-1.20], respectively). Concerning suspected drugs, systemic antibiotics (n=3318, 68%) were mostly reported with a reporting odds ratio (ROR) and 95% CI of 2.35 [2.20-2.51]. In the case of antibiotic-induced anaphylaxis, the third-generation cephalosporins were predominant (n=1961, 40.2%, ROR 2.39 [2.24-2.55]). We also noted drugs generally associated with DIA such as contrast agents (ROR 2.43 [2.04-2.88]) and anaesthetics (ROR 4.02 [3.30-4.89]). Furthermore, unexpected signals were observed for alpha-chymotrypsin (ROR 1.75 [1.23-2.44]) and amoxicillin/sulbactam (ROR 1.59 [1.18-2.10]), uncommonly reported in western countries. In recent years, cases of drug-induced DIA have increased in Vietnam, mostly due to antibiotics and third-generation cephalosporins. The inappropriate use of these drugs should be taken into account. Our findings also highlighted typical Vietnamese signals for alpha-chymotrypsin- and amoxicillin/sulbactam-induced anaphylaxis, which may relate to a specific sociological context in resource-limited countries.

Evaluation of the Potential Risk Factors for Drug-Induced Anaphylaxis in Adult Patients

Aim: To investigate the potential risk factors in patients who have experienced anaphylaxis from drugs. Method: The study included 281 adult patients (median age 40 years; 76.5% female) who experienced immediate types of hypersensitivity reaction to a drug. The patients were divided into an anaphylaxis group and a nonanaphylaxis group. The anaphylaxis group was diagnosed according to the criteria of the World Allergy Organization. Skin testing with culprit drugs was performed. In the nonanaphylaxis group, drug provocation tests were performed with culprit drugs, including aspirin or diclofenac, to determine nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Atopy was determined by skin prick tests with the common inhalant allergens. Patients’ demographics, clinical features, and baseline tryptase and total IgE levels were compared between the 2 groups. Results: The median interval between the last reaction in the patient’s history and the study evaluation was 7 months (range 1–120 months). In 52.3% of the patients, reactions were defined as anaphylaxis. The most common culprit drugs were NSAIDs (56.9%) and β-lactams (34.7%). The culprit drugs were used parenterally in 13.2% of the patients. 34.9% of the patients had comorbid diseases and 24.6% used additional drugs, the most common being antihypertensives (10%). Atopy was determined in 28.8% and 28.1% of the patients were smokers. The median serum level of baseline tryptase and total IgE was 3.5 µg/L and 77 kU/L, respectively. In 46.3% of the patients, skin tests with culprit drugs were positive and the positivity ratio was higher in the anaphylaxis group (p = 0.002). Anapyhlaxis was more common in patients who were: hypertensive, atopic, using angio­tensin-converting enzyme inhibitors/angiotensin receptor blockers, and received the culprit drug parenterally (p = 0.034, p = 0.04, p = 0.03, p = 0.035, p = 0.013, and p < 0.001). In the multivariate analysis, it was observed that the parenteral usage of the drug and the presence of atopy were significantly higher in the anaphylaxis group (p < 0.001, odds ratio [OR] = 20.05, confidence interval [CI] 4.75–88.64; p = 0.012, OR = 2.1, CI 1.17–3.74). Age, smoking, family history, and serum levels of baseline tryptase and total IgE did not differ between groups. Conclusion: The parenteral route and atopy increase the risk of drug-induced anaphylaxis. IgE-mediated sensitivity to the culprit drug seems to facilitate anaphylaxis.

SUCCESSFUL DESENSITIZATION TO PACLITAXEL: A CASE REPORT

Introduction Antineoplastics are the third leading cause of death due to drug-induced anaphylaxis. Taxanes are an integral part of the chemotherapeutic regimen used in gynecological malignancies. Drug desensitization is a therapeutic technique that induces a temporary state of tolerance to a drug responsible for a hypersensitivity reaction. Case Description A 48 year old female diagnosed with stage IV mixed epithelial ovarian cancer and arterial hypertension. Chemotherapy with carboplatin + paclitaxel is indicated, during the first cycle. She presents within the first 5 minutes of application of paclitaxel: lipotimia and wheals, without hypotension, hypoxemia, or wheezing. Skin tests are performed, resulting positive to paclitaxel at dilution 1:1000, a protocol of desensitization was performed based on 6 bags of sodium chloride, and paclitaxel in different concentrations. The desensitization doses were administered within six hours of preparation, and there was no reaction to the administration of the medication. Discussion Hypersensitivity reactions are common with the administration of taxanes. A desensitization protocol was performed, considering it successful since the patient was able to continue her treatment without adverse reactions. Antineoplastics are the third leading cause of death due to drug-induced anaphylaxis. Taxanes are an integral part of the chemotherapeutic regimen used in gynecological malignancies. Drug desensitization is a therapeutic technique that induces a temporary state of tolerance to a drug responsible for a hypersensitivity reaction. A 48 year old female diagnosed with stage IV mixed epithelial ovarian cancer and arterial hypertension. Chemotherapy with carboplatin + paclitaxel is indicated, during the first cycle. She presents within the first 5 minutes of application of paclitaxel: lipotimia and wheals, without hypotension, hypoxemia, or wheezing. Skin tests are performed, resulting positive to paclitaxel at dilution 1:1000, a protocol of desensitization was performed based on 6 bags of sodium chloride, and paclitaxel in different concentrations. The desensitization doses were administered within six hours of preparation, and there was no reaction to the administration of the medication. Hypersensitivity reactions are common with the administration of taxanes. A desensitization protocol was performed, considering it successful since the patient was able to continue her treatment without adverse reactions.

Drug eruption by antihistamine mistaken for chronic urticaria in a child.

Although rare, antihistamines can cause adverse effects, including drug-induced eruptions or anaphylaxis. A 4-year-old child visited the pediatric department of a hospital for skin eruptions after administration of antihistamines, (e.g., ucerax [hydroxyzine] or leptizine [levocetirizine]), for cholinergic rashes; he did not have pruritus. Skin prick, intradermal, and drug provocation tests were performed to determine the relationship between the antihistamines and eruptions. Levocetirizine induced wheals in the skin prick test and a rash in the oral drug provocation test. In contrast, ketotifen induced no reaction in the skin prick test but showed a positive reaction in the oral provocation test. Our case report highlights that children can experience the same types of adverse reactions as seen in adults, and cross-reactivity between various antihistamines can occur.

PO380 Asthma, Asthma Control and Risk of Acute Myocardial Infarction: the Hunt Study

Drug-induced anaphylaxis is a well-known adverse drug reaction for some drug classes, but emerging drug causes of anaphylaxis and novel mechanisms may contribute in unrecognized ways.We sought to determine the top drugs reported in association with anaphylaxis and anaphylaxis followed by death in the Food and Drug Administration Adverse Event Reporting System (FAERS).We reviewed the publicly available FAERS database from 1999 to 2019. Using search terms “anaphylactic shock” or “anaphylactic reaction” and sorting cases by generic drug names, we counted and trended reports to FAERS in which a drug was associated with anaphylaxis or anaphylaxis followed by death.From 1999 to 2019, there were 17,506,002 adverse drug events reported in FAERS, of which 47,496 (0.27%) were reported as anaphylaxis. Excluding patients without age, sex, or country data, respectively, the median age of patients in reports of anaphylaxis was 52 (interquartile range: 28), 62.71% were female, and 13,899 of 34,381 (40.43%) reports were from the United States. There were 2984 of 47,496 (6.28%) reports of anaphylaxis followed by death. Top drug classes associated with anaphylaxis in FAERS were antibiotics, monoclonal antibodies (mAbs), nonsteroidal anti-inflammatory drugs, and acetaminophen. Top drug classes associated with anaphylaxis deaths were antibiotics, radiocontrast agents, and intraoperative agents. Linear regression demonstrated reports of anaphylaxis to mAbs increasing at an average rate of 0.77% of total anaphylaxis reports per year (95% confidence interval: 0.65, 0.88) from 2.00% in 1999 to 17.37% in 2019, faster than any other drug class.Antibiotics were highly reported for anaphylaxis overall and anaphylaxis followed by death. Increasing reports were noted for anaphylaxis to mAb therapies.

Drug-Induced Anaphylaxis with Various Aspects

Drug-Induced Anaphylaxis with Various Aspects

Drug-induced anaphylaxis: seven-year single-center survey.

Background and Objective. Drug-induced anaphylaxis (DIA) is the most common cause of fatal anaphylaxis. We aimed to characterize patients with DIA and their allergological workup. Methods. Systematic review of patients with history of DIA referred to our center over 7 years. Results. Included 125 patients (10% pediatric age), being 36 years the median age of first episode (from 1 to 74 years). The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (43%), antibiotics (42%) and anesthetic agents (6%). In 24% the reactions occurred in hospital setting and 14% perioperative. The etiology was confirmed in 75% through allergological workup. Conclusions. NSAIDs and antibiotics were responsible for most of DIA. The heterogeneity of mechanisms, the severity of the reactions and the lack of standardized in vivo and/or in vitro tests for some drugs do not allow to confirm the diagnosis in all cases. Patients with DIA should be evaluated in specialized centers to perform accurate diagnosis, to prevent recurrence and to find safe alternatives.

Drug-Induced Anaphylaxis Documented in Electronic Health Records

Although drugs represent a common cause of anaphylaxis, few large studies of drug-induced anaphylaxis have been performed. To describe the epidemiology and validity of reported drug-induced anaphylaxis in the electronic health records (EHRs) of a large United States health care system. Using EHR drug allergy data from 1995 to 2013, we determined the population prevalence of anaphylaxis including anaphylaxis prevalence 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. 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(<1%) anaphylaxis cases and 1,587 patients (8.0%) saw an allergist for follow-up. 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.