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Background: Using the reaction history in logistic regression and machine learning (ML) models to predict penicillin allergy has been reported based on non-US data., Objective: We developed ML positive penicillin allergy testing prediction models from multisite US data., Methods: Retrospective data from 4 US-based hospitals were grouped into 4 datasets: enriched training (1:3 case-control matched cohort), enriched testing, nonenriched internal testing, and nonenriched external testing. ML algorithms were used for model development. We determined area under the curve (AUC) and applied the Shapley Additive exPlanations (SHAP) framework to interpret risk drivers., Results: Of 4777 patients (mean age 60 [standard deviation: 17] years; 68% women, 91% White, and 86% non-Hispanic) evaluated for penicillin allergy labels, 513 (11%) had positive penicillin allergy testing. Model input variables were frequently missing: immediate or delayed onset (71%), signs or symptoms (13%), and treatment (31%). The gradient-boosted model was the strongest model with an AUC of 0.67 (95% confidence interval [CI]: 0.57-0.77), which improved to 0.87 (95% CI: 0.73-1) when only cases with complete data were used. Top SHAP drivers for positive testing were reactions within the last year and reactions requiring medical attention; female sex and reaction of hives/urticaria were also positive drivers., Conclusions: An ML prediction model for positive penicillin allergy skin testing using US-based retrospective data did not achieve performance strong enough for acceptance and adoption. The optimal ML prediction model for positive penicillin allergy testing was driven by time since reaction, seek medical attention, female sex, and hives/urticaria., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: There is no accepted grading system classifying the severity of immediate reactions to drugs., Objective: The purpose of this article is to present a proposed grading system developed through the consensus of drug allergy experts from the United States Drug Allergy Registry (USDAR) Consortium., Methods: The USDAR investigators sought to develop a consensus severity grading system for immediate drug reactions that is applicable to clinical care and research., Results: The USDAR grading scale scores severity levels on a scale of 0 to 4. A grade of no reaction (NR) is used for patients who undergo challenge without any symptoms or signs, and it would confirm a negative challenge result. A grade 0 reaction is indicative of primarily subjective complaints that are commonly seen with both historical drug reactions and during drug challenges, and it would suggest a low likelihood of a true drug allergic reaction. Grades 1 to 4 meet the criteria for a positive challenge result and may be considered indicative of a drug allergy. Grade 1 reactions are suggestive of a potential immediate drug reaction with mild symptoms. Grade 2 reactions are more likely to be immediate drug reactions of moderate severity. Grade 3 reactions have features suggestive of a severe allergic reaction, whereas grade 4 reactions are life-threatening reactions such as anaphylactic shock and fatal anaphylaxis., Conclusion: This proposed grading schema for immediate drug reactions improves on prior schemata by being developed specifically for immediate drug reactions and being easy to implement in clinical and research practice., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Older adults have an increased risk of adverse drug reactions and negative effects associated with alternative antibiotic use. Although the number of antibiotic allergies reported increases with age, the characteristics and outcomes of older adults receiving drug allergy assessment are unknown., Objective: To assess the characteristics and outcomes of drug allergy evaluations in older adults., Methods: We considered patients aged above or equal to 65 years enrolled in the United States Drug Allergy Registry (USDAR), a US multisite prospective cohort (January 16, 2019 to February 28, 2022). Data were summarized using descriptive statistics., Results: Of 1678 USDAR participants from 5 sites, 406 older adults aged above or equal to 65 years (37% 65-69 years, 37% 70-74 years, 16% 75-79 years, and 10% ≥80 years) received 501 drug allergy assessments. USDAR older adults were primarily of female sex (69%), White (94%), and non-Hispanic (98%). Most USDAR older adults reported less than or equal to 1 infections per year (64%) and rated their general health as good, very good, or excellent (80%). Of 296 (59%) penicillin allergy assessments in USDAR older adults, 286 (97%) were disproved. Other drug allergy assessments included sulfonamide (n = 41, 88% disproved) and cephalosporin (n = 20, 95% disproved) antibiotics. All 41 drug allergy labels in USDAR participants aged above or equal to 80 years and all 80 penicillin allergy labels in USDAR men aged above or equal to 65 years were disproved., Conclusion: Older adults represented a quarter of USDAR participants but were neither racially nor ethnically diverse and were generally healthy without considerable antibiotic need. Most older adults presented for antibiotic allergy assessments, the vast majority of which were disproved. Drug allergy assessments may be underutilized in the older adults who are most vulnerable to the harms of unconfirmed antibiotic allergy labels., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: An unconfirmed history of antibiotic allergies may negatively influence prescribing patterns for preoperative antibiotic prophylaxis and increase rates of postoperative wound infections through unnecessary use of alternative antibiotics., Methods: After a literature search, we developed a questionnaire for the structured collection of antibiotic allergy history in the anesthesia consultation center and tested it over 2 years at a tertiary care hospital under everyday conditions as part of a quality assurance project. All data were evaluated completely anonymously in the context of standard care., Results: After refining the questionnaire, we analyzed 4866 recorded optimized questionnaires, of which 51 were incomplete. An antibiotic allergy was denied 4312 times and affirmed 503 times, which corresponds to 10% in our sample. The most frequent single substances or groups in the 503 respondents with a positive history of antibiotic allergy were penicillin in 271 (54%), amoxicillin in 65 (13%), an unknown single agent in 50 (10%) and multiple substances in 25 (5%). The reported event occurred more than 10 years ago in 192 (38%) of the respondents, less than 10 years ago in 116 (23%), and 195 (39%) could not provide information. The time from exposure to symptom onset was less than 1h in 96 (19%), between 1 and 24 h in 75 (15%), more than 24 h in 106 (21%), and the remainder could not provide information. Allergy-specific treatment was recalled by 75 (15%) respondents, 287 (57%) reported not having received specific treatment, and the remainder could not recall. A specific allergy test was reported by 55 (11%) respondents, 337 (67%) said no allergy test had been made, and the rest could not recall. A substance-specific allergy passport was issued in 80 (16%) respondents. According to expert assessment, symptoms compatible with an IgE-mediated reaction were present in 96 (19%) of the respondents. An IgE-mediated reaction was considered possible in 70 (14%) and could be excluded by history in 337 (67%) of respondents. Out of 503 respondents with a positive history 51 (10%) could not remember the allergic substance but 7 (14%) of the 51 reported symptoms compatible with severe anaphylaxis or anaphylactic shock and 6 of the 51(12%) reported symptoms possibly related to an IgE-mediated reaction., Discussion: Our survey revealed approximately 10% of respondents reporting an antibiotic allergy, which is in the upper range of data published in international literature and corresponds most closely to American data. Thus, the topic is also relevant to German anesthesia consultation centers, given the high rate of respondents who could have been "delabeled" based on the comprehensive assessment of their history. More expert allergy testing is needed in patients who report symptoms related or probably related to an IgE-mediated reaction. In our opinion, a special issue exists in those patients who did not remember the exact antibiotic but reported symptoms compatible with severe anaphylaxis putting them at high risk of unintended re-exposure., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

A diverse group of Food and Drug Administration-approved cationic drugs including antibiotics, neuromuscular blocking drugs, opioids, antidepressants, and radiocontrast media activate mast cells and cause hypersensitivity reactions by both an immunoglobulin E IgE-dependent and independent manner. The recent discovery that these drugs activate mast cells via the G protein-coupled receptor known as Mas-related GPCR-X2 (MRGPRX2) has represented a paradigm shift of how drug hypersensitivity reactions are viewed. This article provides an overview of the current status of the role of MRGPRX2 on non-IgE-mediated drug hypersensitivity. Potential risk factors and evaluation for suspected MRGPRX2-mediated drug reactions are also discussed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Intravenous (IV) iron is the therapy of choice when oral iron is ineffective or poorly tolerated, yet use has been limited by fears of hypersensitivity reactions (HSRs). Newer formulations that bind iron more tightly and release it more slowly have made the risk of serious or severe HSRs very low. One such formulation, ferric derisomaltose, has been approved in the United States for delivery of 1000 mg iron in a single IV infusion. Ferric derisomaltose rapidly repletes iron parameters with low rates of serious or severe HSRs. Single-infusion iron repletion offers convenience, eliminates adherence concerns, and reduces healthcare resource utilization., (© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Background: Penicillin allergy is frequently reported. In pregnant women, reported penicillin allergy is associated with negative health outcomes and suboptimal group B streptococcal prophylaxis. For individuals having penicillin allergy, skin testing followed by an observed oral challenge is recommended. Previous data indicate a low risk of adverse reaction with skin testing in pregnant women, but the subsequent oral challenge was not routinely pursued., Objective: To determine whether skin testing followed by the outpatient oral challenge is tolerated by pregnant women., Methods: We conducted a retrospective review of all pregnant women who underwent penicillin allergy evaluation at an outpatient allergy and clinical immunology clinic. The patients underwent oral amoxicillin challenges based on the discretion of the allergy provider. We evaluated the index reaction history, skin test results, oral challenge results, and subsequent antibiotic exposure., Results: A total of 46 pregnant women underwent skin testing without adverse reactions, of whom 44 patients (95.6%) received negative results. A total of 18 women (39%) completed an oral challenge without adverse reactions. Patients challenged vs not challenged did not differ in patient age, gestational age, latency since index reaction, or reaction history risk level. Notably, 28 women received intrapartum antibiotics. There was no difference in intrapartum antibiotic administration between those who did or who did not complete an in-office oral challenge (P = .90)., Conclusion: Penicillin skin testing and oral challenge in pregnant women can safely be performed in the outpatient setting. There was no difference in the intrapartum antibiotic use between women who were and those who were not challenged. Further research is needed to determine the utility of oral challenge in pregnant patients., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Data are lacking with concern to the prevalence and management of aspirin (ASA) hypersensitivity. Objective: To study the prevalence, different types of reactions, and implications for clinical management of ASA hypersensitivity in a cardiology practice. Methods: We conducted an electronic medical record review of 11,375 individuals, 5052 (44%) in the ambulatory setting, and 6323 (56%) admitted for percutaneous coronary intervention (PCI), from January 2012 to December 2013. Results: The prevalence of ASA hypersensitivity was 1.88% (n = 214). Skin reactions were the most common (40 [19%]), followed by angioedema (10 [4.6%]), respiratory (9 [4.2%]), and anaphylaxis (6 [2.8%]). No records were found for 74 patients (34.5%), and 69 patients (32.2%) were mistakenly labeled as allergic for having gastrointestinal symptoms. Of the 214 patients who had documented ASA hypersensitivity, 108 individuals (50.46%) had coronary artery disease. The medications at discharge were the following: ASA (30 [14%]), thienopyridine (48 [22%]), a combination of ASA and thienopyridine (13 [6%]), anticoagulation only (26 [12%]), and no antiplatelet (97 [43%]). Conclusion: ASA hypersensitivity is often not documented correctly or is often misdiagnosed or not appropriately managed. There is a need for improved management of ASA hypersensitivity, including appropriate referral for ASA desensitization and combating unnecessary avoidance in patients with intolerance due to adverse effects.

Background: Antibiotic allergies, especially penicillin, are the most frequent drug allergy listed in the medical record. Proactive evaluations of antibiotic allergies, particularly penicillin allergies, have been recommended by various specialty societies. Objective: To review the history of the discovery of penicillin, implications of the penicillin allergy label, various delabeling strategies as well as a brief overview of the approach to cephalosporin, fluoroquinolone, and macrolide allergy. Methods: Recent studies on penicillin allergy delabeling and on cephalosporin and fluoroquinolone allergies were reviewed. Results: Although Alexander Fleming is often solely credited with the discovery of penicillin, other scientists were critical to the development of penicillin as a life-saving antibiotic. The vast majority of patients with a penicillin allergy label are not allergic; however, this label results in increased morbidities and mortality. A variety of penicillin delabeling strategies can be used in both the outpatient and the inpatient settings. The role of direct penicillin challenge in patients at low risk is emerging and is the method of choice for children. Patients with an unconfirmed penicillin allergy have a low risk of reacting to cephalosporins. The R1 side chain largely dictates cephalosporin allergy and cross-reactivity. Drug challenge is the preferred method for evaluation of both fluoroquinolone and macrolide allergy. Conclusion: Multiple effective methods are available to delabel patients of common antibiotic allergies. Delabeling patients in a proactive manner can reduce patient morbidity.

Background: 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., Objective: To describe e-consult use at an academic allergy/immunology practice., Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The risk for developing immediate or delayed hypersensitivity reactions to radiocontrast media (RCM) interferes with the diagnosis and treatment of a number of patients requiring imaging diagnostic methods for many common diseases. A group of experts met in Orlando, Florida, in March 2018 to analyze the similarities and differences in the management of RCM reactions in different areas of the world. This paper presents a summary of the recommendations provided by this consensus group, highlighting controversial issues and unmet needs that require further research., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Drug allergy pathways are standardized approaches for patients reporting prior drug allergies with the aim of quality improvement and promotion of antibiotic stewardship. At the International Drug Allergy Symposium during the 2018 American Academy of Allergy, Asthma, and Immunology/World Allergy Organization Joint Congress in Orlando, Florida, drug allergy pathways were discussed from international perspectives with a focus on beta-lactam allergy pathways and pragmatic approaches for acute care hospitals. In this expert consensus document, we review current pathways, and detail important considerations in devising, implementing, and evaluating beta-lactam allergy pathways for hospitalized patients. We describe the key patient and institutional factors that must be considered in risk stratification, the central feature of pathway design. We detail shared obstacles to widespread beta-lactam allergy pathway implementation and identify potential solutions to address these challenges., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Unconfirmed penicillin allergy poses substantial public health consequences. The most widely accepted protocol to evaluate penicillin allergy is skin testing followed by an amoxicillin challenge., Objective: To evaluate the safety of direct oral graded challenges to amoxicillin., Methods: A prospective single-blind clinical trial with historical controls of patients ≥7 years old with historical non-life-threatening reactions to penicillin was conducted. Patients received placebo followed by a 2-step graded challenge to amoxicillin. The allergic reaction rate was compared with the rate observed in our previous study that included skin testing and with the currently reported penicillin allergy prevalence in the US population., Results: Of the 155 participants who completed an amoxicillin challenge, 120 patients (77.4%) experienced no reaction whereas 31 patients (20%) experienced nonallergic reactions to either placebo (n = 16) or amoxicillin (n = 15). Four patients (2.6%) developed mild allergic reactions. Significantly (P = .03) fewer patients (4 of 155, 2.6%, 95% confidence interval [CI]: 1.0%, 6.5%) were determined to be allergic compared with 14 of 170 subjects (8.2%, 95% CI: 5.0%, 13.4%) in our previous study where patients were determined to be allergic based on either positive skin tests (n = 11) or allergic challenge reactions after negative skin tests (n = 3). This 2.6% reaction rate was also significantly less than the 10% reported US prevalence of penicillin allergy (P = .003)., Conclusions: Placebo-controlled oral graded challenges to amoxicillin without prior skin testing may be safe for patients ≥7 years old with non-life-threatening historical reactions to penicillin. Amoxicillin can be tolerated by the majority of patients with self-reported penicillin allergy., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: A history of penicillin allergy is associated with an increased risk of nosocomial infections because patients are exposed to non-beta lactam antibiotics. Ruling out inaccurate penicillin allergy during hospitalization decreases prescription of beta lactam antibiotics. However, the utilization of penicillin allergy testing and timeliness in relation to initiation of antibiotics is not known., Objective: Our aim was to describe the proportion and characteristics of patients who underwent inpatient penicillin allergy testing in a hospital without a guideline or infrastructure for inpatient penicillin allergy testing., Methods: We performed a retrospective chart review of patients admitted to our institution between January 1, 2008, and December 31, 2015, who underwent penicillin allergy testing., Results: Forty-nine patients were identified; 27 (55.1%) were women. The median age was 61.5 years (interquartile range [IQR], 48.5-71 years). The median Charlson-Comorbidity index score was 4 (IQR, 2-5.5). Of these patients, 42.86% (21) were admitted to the intensive care unit, 79.6% of allergy consults were requested by infectious disease physicians, and 87.8% of patients were receiving non-beta lactam antibiotics at the time of testing. The patients received a median of 5 days of antibiotics before testing (range, 0-16 days; IQR, 3-7 days). Antimicrobial therapy was changed in 78.0% of the patients (32), of whom 68.3% (21/32) was attributable to penicillin allergy testing., Conclusion: Inpatient penicillin allergy testing is a critical component of antibiotic stewardship; however, an adequate infrastructure is essential for timely evaluation. Inpatient penicillin allergy evaluation requires a multidisciplinary approach focused on patient selection; risk stratification; and optimization of a timely, safe, and cost-effective approach to optimize patient outcomes.

Background: The epidemiology of allergic drug reactions is poorly understood due, in large part, to difficulty in identifying true cases in population data sets. Use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes is a potentially valuable approach that requires formal evaluation., Objective: To better understand the utility of ICD-9-CM codes for identification of allergic drug reactions, including the validation of specific codes by chart review., Methods: We reviewed randomly sampled medical records of patients treated in the emergency department (ED) between January 1, 2001, and December 31, 2006, with ICD-9-CM codes for drug allergy and E codes (E930-949) for adverse drug reactions., Results: During the 6-year period, 11,130 charts were identified by ICD-9-CM and E codes and 1,634 were reviewed. Allergic drug reactions were found in 444 (27%) of the reviewed ED visits. The codes that identified the highest percentage of true allergic drug reactions were dermatitis due to drug (693.0; 87%), adverse reaction to drug (995.2; 52%), and anaphylaxis (995.0; 38%). Patients with both an ICD-9-CM code and an E code had a high likelihood of having an allergic drug reaction (76%). Most allergic drug reactions were attributed to antibiotics (42%), intravenous contrast (7%), and nonsteroidal anti-inflammatory drugs (6%). The estimated frequency of allergic drug reactions increased from 0.49% of ED visits in 2001 to 0.94% in 2012., Conclusions: Specific ICD-9-CM and E codes can be used in combination to identify allergic drug reactions. Further study of these codes in the inpatient and outpatient settings is necessary to better understand the utility of diagnosis codes for improving epidemiologic research on drug allergy., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Allergic reactions to drugs are a serious public health concern. In 2013, the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Diseases sponsored a workshop on drug allergy. International experts in the field of drug allergy with backgrounds in allergy, immunology, infectious diseases, dermatology, clinical pharmacology, and pharmacogenomics discussed the current state of drug allergy research. These experts were joined by representatives from several National Institutes of Health institutes and the US Food and Drug Administration. The participants identified important advances that make new research directions feasible and made suggestions for research priorities and for development of infrastructure to advance our knowledge of the mechanisms, diagnosis, management, and prevention of drug allergy. The workshop summary and recommendations are presented herein., (Published by Elsevier Inc.)

Diagnostic criteria and administrative codes for anaphylaxis have evolved in recent years, partly reflecting the challenges in recognizing anaphylaxis and understanding its symptoms. Before the diagnostic criteria were disseminated by the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network, several studies showed that a substantial proportion of anaphylaxis cases presenting to the emergency department (ED) were not recognized as such. Furthermore, epinephrine, the first-line treatment, was used in fewer than half of cases, especially if anaphylaxis was not diagnosed at the time. Although management practices may have improved since that time, anaphylaxis continues to be underrecognized and undertreated in the US. Of particular concern are findings that the majority of patients who visited the ED for an acute allergic reaction or anaphylaxis were not given a prescription for an epinephrine autoinjector, educated about avoiding the offending allergen, or advised to consult with an allergist. Improvements in the recognition and management of anaphylaxis have the potential to reduce the substantial burden that it currently places on the health care system. The articles in this supplement cover a wide range of issues surrounding anaphylaxis and seek to disseminate information helpful to health care professionals in general and primary care providers in particular., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The International Classification of Diseases (ICD)-9 included a code only for anaphylactic shock. The improved ICD-10 coding defines the different symptoms and types of anaphylaxis and includes coding for anaphylaxis without shock. This new coding is consistent with the efforts of the National Institute of Allergy and Infectious Diseases (NIAID) and the Food Allergy and Anaphylaxis Network (FAAN), who convened a panel to formulate a definition of and the diagnostic criteria for anaphylaxis. Anaphylaxis is a serious reaction that has a rapid onset and may cause death. It is a systemic immunoglobulin E-mediated reaction resulting from the sudden release of multiple mediators from mast cells and basophils. Foods are the most common triggers for anaphylactic reactions, followed by drugs, insect stings, and idiopathic anaphylaxis (anaphylaxis of unknown cause). If the NIAID/FAAN criteria are met and anaphylaxis is diagnosed, epinephrine administration is mandatory. Delays in epinephrine administration have been associated with fatalities. Patients should have ready access to >1 epinephrine autoinjector in the outpatient setting. An individualized emergency action plan should be developed for each patient at risk for anaphylaxis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The types of agents implicated to trigger intraoperative anaphylactic reactions vary among reports, and there are no recent series from the United States. In this retrospective study, we examined perioperative anaphylactic reactions that occurred at a major tertiary referral academic center., Methods: To characterize perioperative allergens associated with anaphylactic reactions, we reviewed the Mayo Clinic Division of Allergic Diseases skin test database between 1992 to 2010. The records of all patients who were tested for perioperative and anesthetic medications were reviewed. Charts that included a detailed history obtained by an allergist, skin test results, and tryptase measurements when available were reviewed and categorized., Results: Thirty-eight patients were found to have an anaphylactic reaction during anesthesia, of which 18 were immunoglobulin (Ig)E-mediated anaphylactic reactions (likely causative agent identified by skin test), 6 were non-IgE-mediated anaphylactic reactions (elevated tryptase levels and negative skin test), and 14 were probable non-IgE-mediated anaphylactic reactions (tryptase levels normal or not obtained and negative skin test). Of the IgE-mediated anaphylactic reactions, antibiotics were the most prevalent likely causative agent (50%) whereas neuromuscular blocking drugs were implicated as a likely causative agent in 11% of reactions., Conclusion: Antibiotics were the most common likely causative agent associated with IgE-mediated anaphylactic reactions; however, for 52.6% of reactions, a causative agent could not be determined, suggesting a non-IgE-mediated anaphylactic reaction. The undiagnosed allergic reactions place patients at risk of a subsequent reexposure to the same allergen, or lead to unnecessary avoidance of needed medications.

It typically takes many years before an association of a drug with a rare, serious adverse reaction is established. As related to pediatric drug use, evidence is even more erratic, as most drugs are used off labels. To enhance child safety, there is an urgent need to develop robust and rapid methods to identify such associations in as timely a manner as possible. In this chapter, several novel methods, both clinically based pharmacoepidemiological approaches and laboratory-based methods, are described.

Adverse drug reactions (ADRs) result in major health problems in the United States in both the inpatient and outpatient setting. ADRs are broadly categorized into predictable (type A and unpredictable (type B) reactions. Predictable reactions are usually dose dependent, are related to the known pharmacologic actions of the drug, and occur in otherwise healthy individuals, They are estimated to comprise approximately 80% of all ADRs. Unpredictable are generally dose independent, are unrelated to the pharmacologic actions of the drug, and occur only in susceptible individuals. Unpredictable reactions are subdivided into drug intolerance, drug idiosyncrasy, drug allergy, and pseudoallergic reactions. Both type A and B reactions may be influenced by genetic predisposition of the patient

Purpose: Israeli investigators have identified several relatively frequent disorders due to founder point mutations in Persian (Iranian) Jews, who, for nearly three centuries up to the Islamic Revolution of 1979, were completely isolated reproductively., Methods: Using a community-based model previously employed with Tay-Sachs disease prevention, we developed a pilot program for the Persian Jewish community of greater Los Angeles. We screened for mutations responsible for four relatively frequent autosomal recessive conditions in Persian Jews in which effective interventions are available for each: Pseudocholinesterase deficiency (butyryl cholinesterase deficiency); Congenital hypoaldosteronism (corticosterone methyl oxidase II); Autoimmune polyendocrinopathy (autoimmune regulatory element); and Hereditary Inclusion Body myopathy., Results: One thousand individuals volunteered. Mutations were assessed in saliva-derived DNA and were positive for 121/1000 butyryl cholinesterase deficiency; 92/1000 Hereditary Inclusion Body myopathy; 38/1000 corticosterone methyl oxidase II; and 37/1000 autoimmune regulatory element. Ten homozygous individuals (9 butyryl cholinesterase deficiency and 1 Hereditary Inclusion Body myopathy) and 10 "at-risk" couples (seven for butyryl cholinesterase deficiency and one each for the other three disorders) were identified. These frequencies are comparable with those in Israel and indicate an extraordinary level of inbreeding, as anticipated., Conclusions: A carefully planned effort can be delivered to an "increased risk" community if detailed attention is given to planning and organization. However, availability of an effective intervention for those found to be "at-risk" or possibly affected, is essential before embarking.

Background: The intermittent unavailability of penicilloyl-polylysine since September 2000 has focused interest on commercial anti-penicillin IgE fluorometric enzyme immunoassay (FEIA) tests to evaluate penicillin allergy. There has been no published comparison of commercial anti-penicillin IgE FEIAs and penicillin skin testing performed in the United States., Objective: To determine whether the current commercial anti-penicillin IgE FEIAs can replace or augment penicillin skin testing and oral challenges when evaluating individuals with a history of penicillin allergy for future therapeutic penicillin tolerance., Methods: A prospective convenience sample of 150 individuals with a history of penicillin allergy were evaluated between January 23, 2007, and August 4, 2009, with both penicillin skin tests and commercial anti-penicillin IgE FEIAs to penicillin G, penicillin V, and amoxicillin. All individuals with a negative penicillin skin test result underwent oral penicillin class antibiotic challenges. All individuals with a positive anti-penicillin IgE FEIA result also underwent oral penicillin class antibiotic challenges., Results: Six individuals (4.0%; 95% confidence interval [CI], 0.9% to 7.1%) had positive penicillin skin test results, and none had positive FEIA results. Four individuals (2.7%; 95% CI, 0.1% to 5.3%) had positive FEIA results, and none had positive penicillin skin test results. Three individuals (2.0%; 95% CI, -0.2% to 4.2%) had positive oral challenge results, 1 with hives at 6 hours after challenge and 2 with delayed-onset (at >24 hours) nonurticarial rashes, and none had positive FEIA results., Conclusions: The current commercial anti-penicillin IgE FEIAs are not useful in diagnosing penicillin allergy in patients with remote histories of penicillin allergy. Penicillin skin testing and, if the results are negative, an oral challenge remain the criterion standard tests to determine therapeutic penicillin tolerance., (Copyright 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Pharmacists are commonly confronted with patients with a history of sulfonamide allergy. Basic immunologic and clinical data suggest a low likelihood of a patient with a history of sulfonamide hypersensitivity developing an allergic reaction to a non-antimicrobial sulfonamide drug. We conducted a survey to describe the knowledge and attitudes of licensed pharmacists concerning sulfonamide allergy cross-reactivity., Methods: A survey instrument was developed and sent to all licensed pharmacists in the state of Iowa. The survey recorded demographic information and included six patient scenarios designed to elicit responses concerning sulfonamide allergy cross-reactivity with a number of non-antimicrobial sulfonamides., Results: A total of 421 surveys were returned for a 39% response rate. There was a wide discrepancy in approaches to patients with a history of sulfonamide allergy prescribed a sulfonamide containing non-antibiotic. Differences depended on previous history of tolerating the medication in question, the degree of cautionary statements in product literature, and the familiarity the pharmacist had with the product., Conclusion: Our survey suggests a significant diversity in knowledge and attitudes of pharmacists concerning cross-reactivity of sulfonamide antimicrobials and other drugs with a sulfonamide moiety. Depth of training in this area may be an associative factor.

Screening for HLA-B 5701 reduces the risk of developing an abacavir hypersensitivity reaction (ABC HSR) and is recommended in all patients before initiating highly active antiretroviral therapy (HAART) with abacavir. Between September 2007 and March 2008 we conducted a study of the attitudes and practice patterns of HIV providers in the United States to identify barriers to HLA-B 5701 testing in clinical practice. Study participants who completed an educational program could receive HLA-B 5701 test kits for use in their clinical practice. Surveys were administered before and after the educational program. A total of 477 HIV providers registered to participate in the survey, and 134 providers tested a total of 874 HIV-infected subjects, of which 6% (49/874) were HLA-B 5701 positive. Of 433 providers who completed the preeducation survey, 97% indicated that the test provided clinical value and 77% anticipated barriers to testing, with cost/reimbursement the most frequently cited. Among 202 providers who completed the posteducation survey, perceptions of the test's value remained largely unchanged while the proportion of providers who anticipated or encountered barriers to testing decreased. Of providers who used HLA-B 5701 test kits, 86% (115/134) found it "very easy" or "easy" to obtain test results, 95% (127/134) found it "very easy" or "easy" to interpret results, and 89% (119/134) indicated that they planned to continue HLA-B 5701 testing after the study. The results of this study suggest that HLA-B 5701 testing is easy to use in clinical practice and is a valuable tool to help reduce the risk of developing ABC HSR.

Nearly all chemotherapy and biotherapy drugs used in cancer treatment today can cause hypersensitivity reactions. Certain groups of drugs frequently associated with these reactions include the asparaginases, taxanes, platinum compounds, epipodophyllotoxins, and the monoclonal antibodies. Recognizing and managing hypersensitivity reactions are critical when caring for patients receiving these drugs because the reactions are potentially life-threatening. A thorough understanding of the drugs is necessary to assist the nurse in prevention, early recognition, and timely management.

Background: Iodinated X-ray contrast media (CM) are recognized worldwide to be among the safest and most widely used injectable drugs. However, adverse drug reactions (ADRs) may still occur, ranging in severity from minor disturbances to severe and potentially fatal complications., Purpose: To prospectively determine the incidence and characteristics of acute ADRs during clinical utilization of a single nonionic monomeric contrast agent, iopromide, in routine radiological practice in a large number of nonselected patients., Material and Methods: 74,717 patients were enrolled in a prospective international postmarketing surveillance registry with iopromide (Ultravist; Bayer Schering Pharma AG, Berlin, Germany). A standardized questionnaire was used to collect the following patient information from 762 centers in 27 countries: baseline demographics, risk factors, premedication regimen, type of examination, route of injection, volume and selected concentration of iopromide, and overall tolerance to CM (utilizing specific criteria and descriptors)., Results: The overall rate of ADRs, including tolerance indicators (TI) (i.e., heat sensation and pain at the injection site), was 2%; when TIs were excluded, the rate was 1.5%. Fourteen serious adverse reactions were reported (rate 0.02%), of which none were fatal. There was a higher incidence of ADRs among women and for the age group ranging between 18 and 30 years. Patients with established risk factors, such as a history of previous CM reaction or allergic diathesis (7.4% and 4.1%, respectively), were at an increased risk for developing an ADR when compared to patients without risk factors (1.2%). The incidence of ADRs was not altered by the use of premedication., Conclusion: The safety of iopromide in routine clinical practice was shown to be comparable to the published safety profiles of other nonionic iodinated contrast agents. Adverse drug reaction rates were affected by age, gender, and risk factors (especially previous CM reactions or allergies), but not by premedication.

Drug hypersensitivity reactions are the adverse effects of drugs taken at a dose which is tolerated by normal subjects, and which clinically resemble allergy. There is few true epidemiological data on drug hypersensitivity reactions. The available information requires a cautious interpretation as they are rarely proven. Both under diagnosis and over diagnosis must be taken into account. Drug hypersensitivity reactions represent one third of adverse drug reactions, can be life threatening and motivate changes on drug prescription. They concern more than 7% of the general population, therefore being an important public health problem. A few risk factors are already pinpointed. Future progress in genetics can help the identification of populations at risk for specific reactions. This review describes currently known data on incidence,prevalence, mor tality and risk factors of these reactions.

Proper diagnosis of adverse drug reactions, although often complicated and difficult, is important for the patient and the physician. Often the question of whether it is safe to readminister a medication is an important clinical judgment that needs to be made. Alternative medications may be less effective or have greater toxicities or cost, or both. Areas of ongoing research to improve diagnostic precision for allergic drug reactions include further understanding of the immunochemistry of allergenic medications, improvement of the reproducibility and sensitivity of relevant in vitro assays, and further validation of computer-assisted evaluation of adverse drug events. The positive and negative predictive values for these diagnostic tests need to be better defined whenever possible. At present, the primary diagnostic tool for properly assessing immunologic drug reactions remains a meticulous and detailed history obtained by an astute, knowledgeable, and motivated physician.

In January 2003, leadership of the Medicare National Surgical Infection Prevention Project hosted the Surgical Infection Prevention Guideline Writers Workgroup meeting. The objectives were to review areas of agreement among the published guidelines for surgical antimicrobial prophylaxis, to address inconsistencies, and to discuss issues not currently addressed. The participants included authors from most of the published North American guidelines for antimicrobial prophylaxis and several specialty colleges. The workgroup reviewed currently published guidelines for antimicrobial prophylaxis. Nominal group process was used to draft a consensus paper that was widely circulated for comment. The consensus positions of the workgroup include that infusion of the first antimicrobial dose should begin within 60 minutes before surgical incision and that prophylactic antimicrobial agents should be discontinued within 24 hours of the end of surgery. This advisory statement provides an overview of other issues related to antimicrobial prophylaxis including specific suggestions regarding antimicrobial selection.

Adverse drug reactions (ADRs) are underreported and consequently are an underestimated cause of morbidity and mortality. Recent epidemiologic evidence estimates that ADRs represent the fourth to the sixth leading cause of death. Public awareness is increasing as reports of ADRs and medication errors become more prevalent in the lay press. Reducing the number of ADRs can be accomplished by systems changes made at an individual and national level. At the individual level, increased diligence should be used with regard to reporting and documenting ADRs. At the national level, ADRs can be reduced by expanding the role of the arm of the Food and Drug Administration (FDA) responsible for postmarketing surveillance.

In spite of increasing awareness of latex allergy in the medical and lay communities, many of our colleagues are still not sufficiently knowledgeable about this condition. In these cases, the allergist-immunologist should serve not only as a physician consultant but also as a patient advocate. Letters, phone calls, and/or personal appearances before school boards, employers, patient care committees, infection control committees, medical groups, and industrial representatives may be necessary to protect patients with this condition. The transmission of bloodborne diseases is one of the most pressing public health concerns of our time. Latex gloves and condoms have been essential parts of a worldwide strategy to address this issue. Current Food and Drug Administration regulations impose the same water leak standards on all medical gloves, regardless of manufacturing material or method. However, there are, at this time, no latex-free condoms that prevent the transmission of sexually transmitted disease. In our research efforts we must cooperate with our colleagues in infection control and industry to provide effective and nonantigenic barriers to disease transmission.

Any attempt to distinguish allergic drug reactions from other adverse drug reactions (ADRs) can be complicated by the fact that terminology in this area has not been standardized. True allergic reactions are those resulting from immunologic causes, and their prevalence is only 6 to 10% of all ADRs. A number of factors predispose individuals to drug allergies--the recognition of which might aid the healthcare professional in diagnosing these reactions--and other criteria can be helpful in the process. In order to successfully separate pseudoallergic from allergic from other adverse drug reactions, the clinician must proceed with caution and suspicion. When foreseeable allergic reactions cannot be prevented, measures can be taken that might reduce their impact.