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This review summarizes new research developments and clinical practice recommendations for the diagnosis and management of anaphylaxis presented in the Joint Task Force on Practice Parameters 2023 Anaphylaxis practice parameter Update. It is intended to serve as a high-level summary of the 2023 practice parameter, which makes clinically impactful recommendations based on evidence that has emerged since the 2015 practice parameter. We invite clinicians to explore the full 2023 practice parameter to understand the research methods and underlying evidence that have informed the recommendations summarized here. There are new and evolving diagnostic criteria for anaphylaxis, rules for defining elevated tryptase levels, and recognition of signs and symptoms particular to infants and toddlers. The administration of epinephrine should not be used as a surrogate to diagnose anaphylaxis. Risk factors for anaphylaxis should be assessed on a case-by-case basis. Patient counseling and shared decision-making are essential to support patients' treatment decisions and capacity to manage the risk of anaphylaxis at home and in other community settings. Activation of emergency medical services after home epinephrine administration may not be required in all cases, and patients should be engaged in shared decision-making to determine when home management may be appropriate.

This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.

Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants.

B cells generate antibodies that provide protection from infection, but also cause pathology in autoimmune and allergic conditions. Antigen-specific B cells can be detected by binding their surface antibody receptors with native antigens conjugated to fluorescent probes, a technique that has revealed substantial insight into B cell activation and function. This protocol describes the process of generating fluorescent antigen tetramer probes and delineates a process of enriching large samples based on antigen-specificity for high-resolution analyses of the antigen-specific B cell repertoire. Enrichment of tetramer-binding cells allows for detection of antigen-specific B cells as rare as 1 in 100 million cells, providing sufficient resolution to study naive B cells and IgE-expressing cells by flow cytometry. The generation of antigen tetramers involves antigen biotinylation, assessment of biotin:antigen ratio for optimal tetramer loading and polymerization around a streptavidin–fluorophore backbone. We also describe the construction of a control tetramer to exclude B cells binding to the tetramer backbone. We provide a framework to validate whether tetramer probes are detecting true antigen-specific B cells and discuss considerations for experimental design. This protocol can be performed by researchers trained in basic biomedical/immunological research techniques, using instrumentation commonly found in most laboratories. Constructing the antigen and control tetramers takes 12 h, though their specificity should be assessed before experimentation and may take weeks to months depending on the method of validation. Sample enrichment requires ~2 h but is generally time and cost neutral as fewer cells are run through the flow cytometer.

For food-allergic patients, hypoallergenic formulas (HFs) are medically indicated, often a primary component of the diet and essential for patient safety, health, nutrition, and overall well-being. Yet, food allergy is not included among the conditions mandated for coverage under federal health programs and private health insurance. The 2022 infant formula crisis has affected many North American families and has particularly influenced patients with food allergies who rely on a limited number of safe HF brands to safely meet their nutritional needs for growth and development. The current formula shortage further highlights the longstanding difficulties faced by families with food allergies in accessing HF. Within this context, this article focuses on chronic barriers faced by patients with food allergies in accessing HF and proposes potential solutions. Legislation is desperately needed to address HF affordability through changes in insurance reimbursement and disparities in access to HF among individuals with food allergy.

Approximately 15% of adult Canadians with SARS-CoV-2 infection develop lingering symptoms beyond 12 weeks after acute infection, known as post-COVID condition or long COVID. Some of the commonly reported long COVID cardiovascular symptoms include fatigue, shortness of breath, chest pain, and palpitations. Suspected long-term cardiovascular complications of SARS-CoV-2 infection might present as a constellation of symptoms that can be challenging for clinicians to diagnose and treat. When assessing patients with these symptoms, clinicians need to keep in mind myalgic encephalomyelitis/chronic fatigue syndrome, postexertional malaise and postexertional symptom exacerbation, dysautonomia with cardiac manifestations such as inappropriate sinus tachycardia, and postural orthostatic tachycardia syndrome, and occasionally mast cell activation syndrome. In this review we summarize the globally evolving evidence around management of cardiac sequelae of long COVID. In addition, we include a Canadian perspective, consisting of a panel of expert opinions from people with lived experience and experienced clinicians across Canada who have been involved in management of long COVID. The objective of this review is to offer some practical guidance to cardiologists and generalist clinicians regarding diagnostic and treatment approaches for adult patients with suspected long COVID who continue to experience unexplained cardiac symptoms.

International guidelines stipulate that intramuscular (IM) epinephrine (adrenaline) is the first-line treatment for anaphylaxis, with an established good safety profile. The availability of epinephrine autoinjectors (EAI) has greatly facilitated the lay administration of IM epinephrine in community settings. However, key areas of uncertainty remain around epinephrine usage. These include variations in prescribing EAI, what symptoms should prompt epinephrine administration, whether emergency medical services (EMS) need to be contacted after administration, and whether epinephrine administered via EAI reduces mortality from anaphylaxis or improves quality of life measures. We provide a balanced commentary on these issues. There is increasing recognition that a poor response to epinephrine, particularly after 2 doses, is a useful marker of severity and the need for urgent escalation. It is likely that patients who respond to a single epinephrine dose do not require EMS activation or emergency department transfer, but data are needed to demonstrate the safety of this approach. Lastly, patients at risk of anaphylaxis must be counseled against over-reliance on EAI alone.

Allergy/immunology specialists in the United States prescribing allergy immunotherapy (AIT) have placed a heavy value on practical experience and anecdotal evidence rather than research-based evidence. With the extensive research on AIT conducted in the last few decades, the time has come to better implement evidence-based medicine (EBM) for AIT. The goal of this review was to critically assess EBM for debated concepts in US AIT practice for respiratory allergies in the context and quality of today’s regulatory standards. Debated topics reviewed were the efficacy and safety of AIT in various subgroups (eg, polyallergic patients, older patients, patients with asthma, and pregnant women), diagnosis topics (eg, skin prick test vs allergen-specific serum IgE, factors affecting skin prick tests, use of nasal or conjunctival allergen challenges, and telemedicine for diagnosis), and dosing topics (eg, optimal dosing for subcutaneous immunotherapy and sublingual immunotherapy tablets, US liquid allergen extract history, duration of treatment, and biomarkers of efficacy). In addition, EBM for patient-centered AIT issues (eg, adherence, use of practice guidelines, and pharmacoeconomics) and the approach to implementation of AIT EBM in future clinical practice were addressed. The EBM for each concept was briefly summarized, and when possible, a practical, concise recommendation was given.

Diphenhydramine is one of the most widely available, longest-used antihistamine medications but has many side effects including sedation and risk of toxicity in overdose including cardiac toxicity. It is frequently inappropriately used when newer, more favorable antihistamine medications are available. Second-generation antihistamines are also widely available and affordable, with many of the same desired effects as diphenhydramine and fewer, if any, of the undesirable side effects. Because of the negative side effects and wide availability of alternative antihistamine medications, it is definitively time to move on from diphenhydramine.

Topical corticosteroids are widely used as a treatment for itch and wheals (urticaria), but their benefits and harms are unclear.

Given the increasing prevalence of food allergy, schools and food service establishments must have procedures in place to accommodate those with the condition. Training staff on allergy management has been shown to improve knowledge and skills, although more research is needed to better understand its benefits. Furthermore, although there are challenges involved in maintaining unassigned stock epinephrine programs, they have the potential to reduce morbidity and mortality associated with anaphylaxis by improving access to potentially life-saving medication. Finally, food bans in schools may not be an effective part of food allergy management, and other measures should be considered instead.

An unusual case of Mycobacterium avium complex infection occurred in a young adult with no preexisting disease and no evidence of immunodeficiency. There was diffuse interstitial involvement of the lungs [...]

Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell–mediated angioedema), but their benefits and harms are unclear.

Chronic spontaneous urticaria and chronic inducible urticaria are characterized by wheals, angioedema, or both, whereas other conditions such as hereditary angioedema present only with angioedema. The unpredictability of outbreaks, disfigurement, pruritus, and associated sleep and work disturbance can cause a significant impact on quality of life (QoL). Significant breakthroughs in the understanding of these conditions in recent years have led to the development of novel therapies. Assessment of patients with these conditions not only focuses on the clinical activity of the condition, but also on the impact on QoL and disease control with treatment. Patient-reported outcome measures, especially if sufficiently validated, give due prominence to the patient's perspective regarding disease impact and treatment outcomes. This article will review the tools readily available to assess activity, impact, and control in patients with recurrent wheals, angioedema, or both.

Birch, alder, hazel, and oak are members of the birch homologous group based on cross-reactivity toward the birch pollen allergen Betula verrucosa1. Theoretically, allergy to these tree pollens may be treated by immunotherapy with one representative allergen extract.

Some severe asthmatic patients experience frequent bacterial respiratory tract infections, which contribute significantly to their disease burden, and often are attributed to their use of systemic corticosteroids and comorbid bronchiectasis. We report a case of a 58-year-old woman who had prednisone-dependent asthma and exacerbations with intense mixed eosinophilic and neutrophilic bronchitis. Autosomal dominant hyper-IgE syndrome, which is a primary immunodeficiency characterized by elevated IgE, eosinophilia, and recurrent infections, caused by a novel pathogenic mutation in STAT3 was identified as the cause of her airway disease.We believe that this is the first report of the demonstration of an IL-5 driven eosinophilia that is associated with a STAT3 mutation that was treated successfully with an anti-IL5 biological.

In the wake of the COVID-19 pandemic and massive disruptions to daily life in the spring of 2020, in May 2020, the Centers for Disease Control (CDC) released guidance recommendations for schools regarding how to have students attend while adhering to principles of how to reduce the risk of contracting SARS-CoV-2. As part of physical distancing measures, the CDC is recommending that schools who traditionally have had students eat in a cafeteria or common large space instead have children eat their lunch or other meals in the classroom at already physically distanced desks. This has sparked concern for the safety of food-allergic children attending school, and some question of how the new CDC recommendations can coexist with recommendations in the 2013 CDC Voluntary Guidelines on Managing Food Allergy in Schools as well as accommodations that students may be afforded through disability law that may have previously prohibited eating in the classroom. This expert consensus explores the issues related to evidence-based management of food allergy at school, the issues of managing the health of children attending school that are acutely posed by the constraints of an infectious pandemic, and how to harmonize these needs so that all children can attend school with minimal risk from both an infectious and allergic standpoint.

Hereditary angioedema (HAE) is becoming much more genetically complex than was initially considered. Thus, the role of HAE genetics is expanding beyond research laboratories, and the genotyping of subjects suffering from HAE has become diagnostically indispensable in clinical practice. The synthesis and interpretation of the clinical and biochemical analyses to facilitate appropriate genetic test selection has thus also become significantly more complex. With this in mind, an international multidisciplinary group of 14 experts in HAE genetics and disease management was convened in October 2018. The objective was to develop clear, actionable, evidence- and consensus-based statements aiming to facilitate the communication between physicians treating patients with HAE and clinical geneticists, and thus promote the effective use of genetics in the management of the disease. Eleven consensus statements were generated, encompassing considerations regarding the clinical indications for genotyping patients with angioedema, the methods of detection of HAE-causative variants, the variant pathogenicity curation, the genotyping of patients with HAE in the clinic, and genetic counseling. These statements are intended both to guide clinicians and to serve as a framework for future educational and further genetic testing developments as the field continues to evolve rapidly.

Anaphylaxis is an acute systemic allergic reaction that can be life threatening. In adults, the most common causes of anaphylaxis are foods, drugs, and insect stings. This article reviews the definition, classification, evaluation, differential diagnosis, prognosis, complications, and management of anaphylaxis. Tailored for internists, the article focuses on anaphylactic medication allergies. It provides a guide to optimally evaluate and manage patients with antibiotic allergy using a simple, rapid risk stratification technique, graded antibiotic challenge (test dose), and/or allergist-guided drug desensitization. It also reviews other causes of anaphylaxis that internists are likely to encounter, and an approach to their management.

Oral immunotherapy is an emerging experimental treatment for peanut allergy, but its benefits and harms are unclear. We systematically reviewed the efficacy and safety of oral immunotherapy versus allergen avoidance or placebo (no oral immunotherapy) for peanut allergy.

The traditional health care model is focused on diseases (medicine and natural science) and does not acknowledge patients’ resources and abilities to be experts in their own life based on their lived experiences. Improving health care safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people’s values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care.1It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) from guidelines to digital care pathways, (5) embedding Planetary Health, (6) novel classification of rhinitis and asthma, (7) embedding real-life data with population-based studies, (8) the ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) artificial intelligence, (10) the development of digitally enabled, ARIA person-centered care, and (11) the political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases. Knowledge gaps nevertheless exist in how best to approach patient care as a whole. There have been sixteen randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL- 5R, IL-33, and immunoglobulin (Ig)E. This white paper considers the perspectives of experts in various disciplines such as rhinology, allergy, and respirology across Canada, all of whom have unique and valuable insights to contribute on how to best approach patients with upper airway disease from a multidisciplinary perspective. Methods: A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. A national multidisciplinary expert panel of 34 certified specialists was created, composed of 16 rhinologists, 7 allergists, and 11 respirologists who evaluated the 20 original statements on a scale of 1–9 and provided comments. All ratings were quantitively reviewed by mean, median, mode, range, standard deviation and inter-rater reliability. Consensus was defined by relative interrater reliability measures—kappa coefficient ($\kappa$\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\kappa$$\end{document}) value > 0.61. Results: After three rounds, a total of 22 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with upper airway disease. Conclusion: This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of upper airway disease from a multidisciplinary perspective, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years. Graphical abstract:

Hereditary angioedema (HAE) is a rare disease that has significant morbidity and may be potentially fatal because of airway obstruction.

Epinephrine is the first-line treatment for anaphylaxis. Despite this, there have been identified gaps in the management of anaphylaxis including infrequent or delayed use of epinephrine for acute allergic reactions, as well as inadequate epinephrine autoinjector (EAI) training, and prescription rates of these devices for patients at risk. This paper reviews new data, and new problems in recently published literature on EAIs. A database search was conducted for publications between January 2015 and February 2017 using keywords related to EAIs including their functionality and features, carriage, prescription rates, barriers, and side effects. Eligibility criteria included patients at risk for anaphylaxis, caregivers, and health care professionals. Experimental studies and observational studies were included. Of 1,737 potentially relevant articles, 19 were used for analysis. These articles addressed specific aspects of an EAI, including (1) information on features and functionality; (2) prescriptions; (3) training on their use; and (4) carriage and use at the time of reaction by patients, schools, camps, emergency departments, and paramedics. Our review highlights that existing gaps in anaphylaxis management remain unaddressed. Patient needs are largely unmet, and very few studies are being designed to clarify and instill best practice, and to determine how to increase adherence to existing anaphylaxis guidelines through integrated knowledge translation strategies.

Anaphylaxis reactions lie on a spectrum of severity, ranging from relatively mild lower respiratory involvement (depending on the definition of anaphylaxis used) to more severe reactions which are refractory to initial treatment with epinephrine and may rarely cause death. A variety of grading scales exist to characterize severe reactions, but there is a lack of consensus about the optimal approach to define severity. More recently, a new entity called refractory anaphylaxis (RA) has emerged in the literature, characterized by the persistence of anaphylaxis despite initial epinephrine treatment. However, slightly different definitions have been proposed to date. In this Rostrum, we review these definitions as well as data relating to epidemiology, elicitors, risk factors and management of RA. We propose a need to align the different definitions for RA, to improve epidemiological surveillance, advance our understanding of the pathophysiology of RA, and optimize management strategies to reduce morbidity and mortality.

Clinical trials (PALISADE [ARC003], ARTEMIS [ARC010]) proving efficacy and safety of peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) have used double-blind, placebo-controlled food challenges (DBPCFCs) to screen for eligibility and to evaluate efficacy. In routine clinical practice, individuals with peanut allergy do not always undergo food challenges to confirm diagnosis or determine candidacy for treatment.

Several studies have suggested an impact of allergic rhinitis on academic productivity. However, large studies with real-world data (RWD) are not available.

Urticaria or hives is a common skin condition, which can have a significant impact on the individual’s quality of life (QOL) and be challenging to treat. Urticaria is divided into acute and chronic, depending on the duration of symptoms. Though urticaria is associated with many different disorders, routine investigations should be limited and guided by history and physical examination. New advances have been made in the classification of chronic urticaria (CU), monitoring of disease activity, QOL, and treatment. An evidence-based approach should be used in the management of these patients.

Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4+/+ or il4−/− eosinophils. Eosinophils controlled CD103+ dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.

The article offers information on food allergies. It states that food allergy is a reaction caused by the body's immune response to specific proteins found in foods. It mentions that it is in contrast to food intolerance, in which the reaction is caused by the body's inability to digest or absorb certain food components, such as lactose, and which generally requires a larger amount of food to elicit a response.

Little is known about the impact of food labeling on the allergic consumer.

Anaphylaxis is an acute and often severe systemic allergic reaction. The prevalence of food allergy has been increasing and is currently estimated at ∼3.5. Food allergic reactions account for one-third to one-half of anaphylaxis cases worldwide. It is estimated that approximately 30,000 food-related anaphylactic reactions are treated in United States emergency departments (ED) every year resulting in ∼ 2000 hospitalizations and 150 deaths. The increasing rate of foodinduced anaphylactic episodes in the last few decades underlines the existence of major challenges. This review will critically appraise current guidelines for the diagnosis as well as the acute and long-term management of food-induced anaphylaxis (FIA). Importantly, it will outline existing challenges and suggest measures to improve outcomes in patients with FIA. We propose that the discovery of novel diagnostic (i.e. biomarkers and predictors) and therapeutic approaches is a major challenge that may be overcome as the mechanisms underlying FIA are better delineated. We further propose that better dissemination, implementation and compliance with the consensus management guidelines are urgently needed. This will require education of ED personnel, patient empowerment as well as effective multilateral communication among patients, emergency and family physicians, allergists and specialized volunteer organizations.

We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) in 2004.

Up to 10% of the population reports an “allergy” to penicillin, whereas approximately 1.1% has positive penicillin skin test results. Where penicillin skin tests are unavailable, some have advocated using history to decide whether to use a penicillin-related antibiotic.

Current forms of peanut oral immunotherapy (OIT) are associated with side effects, and there is a lack of evidence addressing how to mitigate them.

Data on the clinical and demographic features of Canadian patients with hereditary angioedema (HAE) are lacking.

An unusual case of Mycobacterium aviumcomplex infection occurred in a young adult with no preexisting disease and no evidence of immunodeficiency. There was diffuse interstitial involvement of the lungs which suggested an active alveolitis. Diagnosis required open-lung biopsy. Restriction fragment length polymorphism analysis and multilocus enzyme electrophoresis indicated that the source of the infection was a hot tub. The infection proved to be exceptionally responsive to treatment, and there was complete resolution with a four-drug regimen.

Allergic rhinitis (AR) is an immunoglobulin (Ig) E–mediated inflammatory condition that causes sneezing, nasal congestion, rhinorrhea, and nasal itch. Although subcutaneous immunotherapy for the treatment of AR has been in use and well established as a treatment modality, sublingual immunotherapy (SLIT) is increasingly considered to be the safer and more convenient alternative. Thus, the objective of this review is to describe recent findings pertaining to the use of SLIT tablets (SLIT-T) for AR.

Hereditary angioedema (HAE) is associated with decreased quality of life (QoL), which has typically been measured using a generic non-disease specific questionnaire.

Community use of epinephrine for the treatment of anaphylaxis is low. Knowledge of rates of epinephrine use in the pre–hospital setting along with identification of barriers to its use will contribute to the development of policies and guidelines.