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Purpose of Review: Perioperative anaphylaxis has historically been attributed to IgE/FcεRI-mediated reactions; there is now recognition of allergic and nonallergic triggers encompassing various reactions beyond IgE-mediated responses. This review aims to present recent advancements in knowledge regarding the mechanisms and pathophysiology of perioperative anaphylaxis., Recent Findings: Emerging evidence highlights the role of the mast-cell related G-coupled protein receptor X2 pathway in direct mast cell degranulation, shedding light on previously unknown mechanisms. This pathway, alongside traditional IgE/FcεRI-mediated reactions, contributes to the complex nature of anaphylactic reactions. Investigations into the microbiota-anaphylaxis connection are ongoing, with potential implications for future treatment strategies. While serum tryptase levels serve as mast cell activation indicators, identifying triggers remains challenging. A range of mediators have been associated with anaphylaxis, including vasoactive peptides, proteases, lipid molecules, cytokines, chemokines, interleukins, complement components, and coagulation factors., Summary: Further understanding of clinical endotypes and the microenvironment where anaphylactic reactions unfold is essential for standardizing mediator testing and characterization in perioperative anaphylaxis. Ongoing research aims to elucidate the mechanisms, pathways, and mediators involved across multiple organ systems, including the cardiovascular, respiratory, and integumentary systems, which will be crucial for improving patient outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Allergic reactions and anaphylaxis occur on a severity continuum from mild and self-limited to potentially life-threatening or fatal reactions. Anaphylaxis is typically a multiorgan phenomenon involving a broad range of effector cells and mediators. Emergency department visits for anaphylaxis are increasing, especially among children. There is a broad differential diagnosis for anaphylaxis, and the diagnosis of anaphylaxis can be aided by the use of the National Institutes of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network clinical diagnostic criteria. Risk factors for severe anaphylaxis include older age, delayed epinephrine administration, and cardiopulmonary comorbidities., Competing Interests: Disclosure Dr. Campbell is an author for UpToDate and a consultant for Bryn Pharma. Dr. Dribin has received research funding from the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number 2UL1TR001425-05A1 and Award Number 2KL2TR001426-05A1., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Anaphylaxis is a potentially life-threatening, multisystem allergic reaction that can cause airway, breathing, or circulatory compromise. Intramuscular epinephrine is the immediate treatment of all patients. Intravenous epinephrine should be used in patients in shock, either as a bolus or infusion, along with fluid resuscitation. Airway obstruction must be recognized, and early intubation may be necessary. For shock that is refractory to epinephrine, additional vasopressors may be needed. Disposition depends on patient presentation and response to treatment. Mandatory observation periods are not necessary, because biphasic reactions are difficult to predict and may occur outside of typical observation periods., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Anaphylaxis is a potentially deadly condition that requires emergent therapy. While frequently treated in the emergency department (ED), recent evidence updates may improve the diagnosis and management of this condition., Objective: This paper evaluates key evidence-based updates concerning the diagnosis and management of anaphylaxis for the emergency clinician., Discussion: The presentation of anaphylaxis can vary. Current diagnostic criteria can be helpful when evaluating patients for anaphylaxis, though multiple criteria exist. While the most common causes of anaphylaxis include medications, insect venom, and foods, recent literature has identified an IgE antibody response to mammalian galactose alpha-1,3-galactose, known as alpha-gal anaphylaxis. Epinephrine is the first-line therapy and is given in doses of 0.01 mg/kg (up to 0.5 mg in adults) intramuscularly (IM) in the anterolateral thigh. Intravenous (IV) epinephrine administration is recommended in patients refractory to IM epinephrine and IV fluids, or those with cardiovascular collapse. Antihistamines and glucocorticoids should not delay administration of epinephrine and do not demonstrate a significant reduction in risk of biphasic reactions. Biphasic reactions may affect 1-7% of patients with anaphylaxis. Risk factors for biphasic reaction include severe initial presentation and repeated doses of epinephrine. Disposition of patients with anaphylaxis requires consideration of several factors., Conclusions: Emergency clinicians must be aware of current updates in the evaluation and management of this disease., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier Inc.)

Although hypothermia has received substantial attention as an indicator of severity in anaphylaxis, it has been neglected from the perspective of whether it could act as a disease-modifying factor in this condition. Here, the impact of naturally occurring (spontaneous) hypothermia on anaphylaxis was evaluated in a murine model of ovalbumin (OVA)-induced allergy. Nonextreme changes in the ambient temperature (T a ) were used to modulate the magnitude of spontaneous hypothermia. At a T a of 24°C, challenge with OVA intraperitoneally or intravenously resulted in a rapid, transient fall in body core temperature, which reached its nadir 4-6°C below baseline in 30 min. This hypothermic response was largely attenuated when the mice were kept at a T a of 34°C. The T a -dependent attenuation of hypothermia resulted in a survival rate of only 30%, as opposed to survival of 100% in the condition that favored the development of hypothermia. The protective effect of hypothermia did not involve changes in the rate of mast cell degranulation, as assessed by the concentration of mast cell protease-1 in bodily fluids. On the other hand, hypothermia improved oxygenation of the brain and kidneys, as indicated by higher NAD + /NADH ratios. Therefore, it is plausible to propose that naturally occurring hypothermia makes organs more resistant to the anaphylactic insult., (Copyright © 2021 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Introduction: Platelet-activating factor (PAF) has a direct role as a mediator in the pathogenesis of various disorders with an inflammatory component, including those with allergic aetiology. The peripheral blood concentration of PAF is dynamically regulated by plasma PAF acetylhydrolase (PAF-AH). Previous research suggest that low activity of plasma PAF-AH could be a predictive marker for increased severity of some types of allergic hypersensitivity reactions-especially anaphylaxis. The purpose of the study was to evaluate the association between plasma PAF-AH activity and severity in patients with anaphylactic reactions following a wasp or bee sting., Materials and Methods: The study group of 89 patients was divided into two subgroups depending on the increasing severity of the most severe anaphylactic reaction in the past, which was assessed according to the Müller's scale. The first subgroup included participants with a history of hypersensitivity reactions up to grade II. The second subgroup consisted of patients who have experienced at least one grade III or IV reactions in the past. A control group of 20 people was established. Plasma PAF-AH activity was measured using a colorimetric method., Results: It has been observed that plasma activity of platelet-activating factor acetylhydrolase was significantly lower in patients with anaphylaxis history compared to the control group with negative atopic history (on average 21.38 nmol/min/ml for the control group, 9.47 nmol/min/ml for the first subgroup and 10.16 nmol/min/ml for the second subgroup, in both cases p < 0.0001)., Conclusion: The plasma activity of PAF-AH is a promising parameter that can help to distinguish a group of patients not threatened with development of anaphylaxis and not requiring laborious or expensive prophylactic procedures., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To describe the emergency department (ED) triage of anaphylaxis patients based on the Emergency Severity Index (ESI), assess the association between ESI triage level and ED epinephrine administration, and determine characteristics associated with lower acuity triage ESI assignment (levels 3 and 4)., Methods: We conducted a cohort study of adult and pediatric anaphylaxis patients between September 2010 and September 2018 at an academic ED. Patient characteristics and management were compared between Emergency Severity Index (ESI) triage level 1 or 2 versus levels 3 or 4 using logistic regression analysis. We adhered to STROBE reporting guidelines., Results: A total of 1090 patient visits were included. There were 26 (2%), 515 (47%), 489 (45%), and 60 (6%) visits that were assigned an ESI triage level of 1, 2, 3, and 4, respectively. Epinephrine was administered in the ED to 53% of patients triaged ESI level 1 or 2 and to 40% of patients triaged ESI level 3 or 4. Patients who were assigned a lower acuity ESI level of 3 or 4 had a longer median time from ED arrival to epinephrine administration compared to those with a higher acuity ESI level of 1 or 2 (28 min compared to 13 min, p < .001). A lower acuity ESI level was more likely to be assigned to visits with a chief concern of hives, rash, or pruritus (OR 2.33 [95% CI, 1.20-4.53]) and less likely to be assigned to visits among adults (OR, 0.43 [0.31-0.60]), patients who received epinephrine from emergency medical services (OR 0.56 [0.38-0.82]), presented with posterior pharyngeal or uvular angioedema (OR, 0.56 [0.38-0.82]), hypoxemia (OR, 0.34 [0.18-0.64]), or increased heart (OR 0.83 [0.73-0.95]) or respiratory (OR 0.70 [0.60-0.82]) rates., Conclusion: Patients triaged to lower acuity ESI levels experienced delays in ED epinephrine administration. Adult and pediatric patients with skin-related chief concerns were more likely to be to be assigned lower acuity ESI levels. Further studies are needed to identify interventions that will improve ED anaphylaxis triage., Competing Interests: Declaration of Competing Interest R.L. Campbell has been a consultant for Bryn Pharma. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Abstract: Anaphylaxis is defined as a rapid systemic reaction that develops in individuals previously exposed to specific allergens. The new exposure causes systemic cellular degranulation, which in turn leads to cardiovascular and respiratory changes that are fatal if not treated immediately. One of the main problems of this scenario in the forensic field is the determination of a correct post-mortem diagnosis. Traditional methods, such as histopathological examination of the respiratory tract and the use of specific antibodies used in immunohistochemistry, are sensitive but not always specific and therefore do not guarantee a high degree of probability in the diagnosis of anaphylaxis. For this reason, a new and promising research frontier in this field of forensic pathology could be represented by the application of miRNAs as biomarkers, as has been done in other areas of medicine.

Background: Clinical reactions to Oral Food Challenge (OFC) in peanut-allergic individuals have been well-characterised, but rates and phenotypes of symptom recurrence beyond the first hour after objective symptoms are less well-characterised., Objective: To evaluate the rate of new-onset symptoms occurring at least 1 h after stopping OFC in peanut-allergic children and adults undergoing peanut-OFC., Methods: We prospectively collected data relating to adverse events following positive reactions at double-blind, placebo-controlled food challenges (DBPCFC) to peanut in children and adults evaluated for eligibility to participate in two clinical trials (NCT02149719, NCT02665793). The trials included people aged 8 to 45 with primary, IgE-mediated peanut allergy at DBPCFC. The challenge protocol included consumption of a light meal 1 h after reaction., Results: A total of 121 participants (64 children, 57 adults) had immediate, objective symptoms at DBPCFC, 25 (17 children, 8 adults) with anaphylaxis. Thirty-three (27%) had progression or recurrence of symptoms ≥ 1 h after objective clinical reaction, of whom 8 developed anaphylaxis. In 23 cases, the onset of new symptoms was associated with consumption of a light meal. In eight cases, symptoms were limited to a symptomatic postural fall in blood pressure noted in preparation for discharge, without any other new features of an allergic reaction., Conclusions & Clinical Relevance: Progressive or new-onset symptoms ≥1 h following initial allergic reaction at OFC are common and can include orthostatic hypotension. Recurrent symptoms may be temporally associated with food consumption., (© 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Venom-induced anaphylaxis (VIA) is a common, potentially life-threatening hypersensitivity reaction associated with (1) a specific symptom profile, 2) specific cofactors, and 3) specific management. Identifying the differences in phenotypes of anaphylaxis is crucial for future management guidelines and development of a personalized medicine approach., Objective: This study aimed to evaluate the phenotype and risk factors of VIA., Methods: Using data from the European Anaphylaxis Registry (12,874 cases), we identified 3,612 patients with VIA and analyzed their cases in comparison with sex- and age-matched anaphylaxis cases triggered by other elicitors (non-VIA cases [n = 3,605])., Results: VIA more frequently involved more than 3 organ systems and was associated with cardiovascular symptoms. The absence of skin symptoms during anaphylaxis was correlated with baseline serum tryptase level and was associated with an increased risk of a severe reaction. Intramuscular or intravenous epinephrine was administered significantly less often in VIA, in particular, in patients without a history of anaphylaxis. A baseline serum tryptase level within the upper normal range (8-11.5 ng/mL) was more frequently associated with severe anaphylaxis., Conclusion: Using a large cohort of VIA cases, we have validated that patients with intermediate baseline serum tryptase levels (8-11 ng/mL) and without skin involvement have a higher risk of severe VIA. Patients receiving β-blockers or angiotensin-converting enzyme inhibitors had a higher risk of developing severe cardiovascular symptoms (including cardiac arrest) in VIA and non-VIA cases. Patients experiencing VIA received epinephrine less frequently than did cases with non-VIA., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Food allergy is the most common cause of anaphylaxis. Changes in posture during acute reactions can trigger fatal outcomes, but the impact of allergic reactions on the cardiovascular system in nonfatal reactions remains poorly understood., Objective: Our aim was to systematically evaluate changes in cardiovascular function during acute allergic reactions to peanut., Methods: Participants underwent double-blind placebo-controlled food challenge to peanut as part of a clinical trial. Changes in hemodynamic parameters (heart rate, stroke volume, blood pressure, and peripheral blood flow) and electrocardiogram findings during food challenges were assessed using noninvasive continuous monitoring., Results: A total of 57 adults (median age 24 years [interquartile range = 20-29]), 53% of whom were female, participated; 22 (39%) had anaphylaxis. Acute reactions were associated with significant changes in stroke volume (mean decrease of 4.2% [95% CI = 0.8-7.6; P = .03]), heart rate (mean increase 11.6% [95% CI = 8.4-14.8; P < .0001]), and peripheral blood flow (mean increase 19.7% [95% CI = 10.8-28.6; P < .0001]), irrespective of reaction severity. These changes were reproduced at a subsequent repeat peanut challenge in 26 participants, and could be reversed with administration of intravenous fluids which resulted in faster resolution of abdominal symptoms., Conclusions: In this first detailed human study of cardiovascular changes during food-induced allergic reactions, we found evidence for significant fluid redistribution, independent of reaction severity. This provides a sound rationale for optimizing venous return during significant allergic reactions to food. Finally, these data provide a new paradigm for understanding severity in anaphylaxis, in which poor outcomes may occur as a result of a failure in compensatory mechanisms., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

This second joint document, written by experts from the Brazilian Association of Allergy and Immunology (ASBAI) and Brazilian Society of Anesthesiology (SBA) concerned with perioperative anaphylaxis, aims to review the pathophysiological reaction mechanisms, triggering agents (in adults and children), and the approach for diagnosis during and after an episode of anaphylaxis. As anaphylaxis assessment is extensive, the identification of medications, antiseptics and other substances used at each setting, the comprehensive data documentation, and the use of standardized nomenclature are key points for obtaining more consistent epidemiological information on perioperative anaphylaxis., (Copyright © 2020. Publicado por Elsevier Editora Ltda.)

The term anaphylaxis describes a severe, potentially life-threatening allergic reaction. It is caused by an acute, systemic immune response to substances against which in most cases a previous sensitization has taken place. An anaphylactic reaction can affect every organ system of the human body. The first signs of an allergic shock are symptoms such as hypotension, tachycardia, exanthema and dyspnea. The complete expression of anaphylactic shock can occur very quickly. A perioperative anaphylaxis, in particular, is not always easy to recognize. Therefore, it is important to know the possible perioperative triggers of anaphylaxis, for instance neuromuscular blocking agents and antibiotics. The treatment has to be initiated quickly to save the life of the patient. The rapid injection of epinephrine and intravenous fluid administration are most important.

Injection of contrast media is the foundation of invasive and interventional cardiovascular practice. Iodine-based contrast was first used in the 1920s for urologic procedures and examinations. The initially used agents had high ionic and osmolar concentrations, which led to significant side effects, namely nausea, vomiting, and hypotension. Newer contrast agents had lower ionic concentrations and lower osmolarity. Modifications to the ionic structure and iodine content led to the development of ionic low-osmolar, nonionic low-osmolar, and nonionic iso-osmolar contrast media. Contemporary contrast agents are better tolerated and produce fewer major side effects., Competing Interests: Disclosure The authors have no disclosures to report in regard to the content of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Food allergy encompasses a range of food hypersensitivities. Different clinical phenotypes for food allergy likely exist in much the same way as endotype discovery is now a major research theme in asthma. We discuss the emerging evidence for different reaction phenotypes (ie, symptoms experienced after allergen exposure in food allergic individuals) and their relevance for clinical practice., Data Sources: Published and unpublished literature relating to reaction phenotypes in food allergy., Study Selections: Authors assessment of the available data., Results: Food anaphylaxis may be pathophysiologically different than anaphylaxis caused by nonfood triggers. Currently, there are no robust, clinically useful predictors of severity in food allergy. It is likely that patient-specific reaction phenotypes exist in food allergy, which may affect the risk of severe anaphylaxis. Allergen immunotherapy may modulate these phenotypes., Conclusion: Data are emerging to confirm our clinical experience that many food allergic patients experience stereotypical symptoms after allergen exposure, both in the community and at supervised oral food challenge, in a manner that varies among patients. Integrating data sets from different cohorts and applying unbiased machine-based learning analyses may demonstrate specific food allergy endotypes in a similar way to asthma. Whether this results in improvements in patient management (eg, through facilitating risk stratification or affecting the decision to prescribe an epinephrine autoinjector and, perhaps, the number of devices) remains to be determined, but given our current inability to predict which patients are most at risk of severe food allergic reactions, this will clearly be an important area of research in the future., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Post-anaphylaxis mast cell anergy (PAMA), commonly referred to as 'empty mast cell (MC) syndrome', is a state of temporary loss of cutaneous MC reactivity in the immediate aftermath of anaphylaxis. Data relating to this condition are sparse and the incidence rate is currently unknown. PAMA has been described only in a few published case reports in the context of hymenoptera venom allergy and perioperative anaphylaxis. Best practice guidelines regarding optimal timing for performing skin tests postanaphylaxis are largely based on expert opinion, and allergy work-up has been recommended after 4-6 weeks postanaphylaxis to avoid false-negative results.This article provides a review of clinical literature surrounding PAMA, critically evaluates intracellular events in MCs from in vitro data and hypothesises regarding plausible immune mechanisms. There are no published data to directly explain molecular mechanisms underlying this phenomenon. Although not evidence based, PAMA has been attributed to depletion of MC granules following anaphylaxis. It is also plausible that exposure to high allergen concentrations in anaphylaxis can induce a temporary shift in MCs towards dominance of inhibitory signalling pathways, thus contributing to a state of transient hyporesponsiveness observed in some patients. Other potential contributory factors for reduced MC reactivity include downregulation of FcεRI expression, cross-linking of FcεRI to the inhibitory, low-affinity IgG receptors and administration of pharmacotherapeutic agents for anaphylaxis treatment. It is likely that this interesting phenomenon can be explained by a combination of these proposed mechanisms in addition to other genetic/host factors that have not yet been identified., Competing Interests: Competing interests: RLB reports grants, personal fees and honoraria for lectures from Thermofisher, Novartis and ALK Abello outside the submitted work. MTK received honoraria for lectures from Thermo Fisher and ALK Abello, outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent studies demonstrated that, in the past few years, the number of jellyfish species is increasing worldwide; this increase can be explained by environmental and climatic reasons. Contacts with jellyfish can cause acute and chronic effects, including allergic reactions. Although anaphylaxis caused by jellyfish is a rare event, repetitive stings during bathing as well as marine sports and job activities represent important risk factors that can increase the probability of sensitization. Recently, it was also pointed out the possibility of anaphylaxis caused by jellyfish ingestion. In these cases, the sensitization could also be related to previous stings. In cases in which there is no history of jellyfish contact or ingestion, it has been hypothesized that there is a sensitization to an unknown cross-reactive antigen. Objective: The purpose of this work was to collect and review published studies and cases of anaphylaxis associated with jellyfish. Methods: We performed a medical literature data base search, which included English language articles published until September 2019, by using the key words "jellyfish" associated with "anaphylaxis" or "anaphylactic shock." Results: The results of our research showed that dangerous reactions can be caused both by contact and ingestion. Moreover, the latest changes in food habits, life style, and globalization could lead to a more frequent exposure to jellyfish both by contact and ingestion, and, consequently, to a higher probability of sensitization. Conclusion: Prospective studies and well-structured research are needed to better understand all the potential immunologic elements of jellyfish, to clarify its role in sensitization, and to avoid possible dangerous allergic reactions caused by cross-reactivity.

Ticks are arthropod ectoparasite vectors of pathogens and the cause of allergic reactions affecting human health worldwide. In humans, tick bites can induce high levels of immunoglobulin E antibodies against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) present in glycoproteins and glycolipids from tick saliva that mediate anaphylactic reactions known as the alpha-Gal syndrome (AGS) or red meat allergy. In this study, a new animal model was developed using zebrafish for the study of allergic reactions and the immune mechanisms in response to tick salivary biogenic substances and red meat consumption. The results showed allergic hemorrhagic anaphylactic-type reactions and abnormal behavior patterns likely in response to tick salivary toxic and anticoagulant biogenic compounds different from α-Gal. However, the results showed that only zebrafish previously exposed to tick saliva developed allergic reactions to red meat consumption with rapid desensitization and tolerance. These allergic reactions were associated with tissue-specific Toll-like receptor-mediated responses in types 1 and 2 T helper cells (T H 1 and T H 2) with a possible role for basophils in response to tick saliva. These results support previously proposed immune mechanisms triggering the AGS and provided evidence for new mechanisms also potentially involved in the AGS. These results support the use of the zebrafish animal model for the study of the AGS and other tick-borne allergies., (Copyright © 2020 Contreras, Pacheco, Alberdi, Díaz-Sánchez, Artigas-Jerónimo, Mateos-Hernández, Villar, Cabezas-Cruz and de la Fuente.)

Background: In some cases, anaphylactic shock (AS) is still lethal, despite rapid use of epinephrine. High doses of epinephrine are associated with severe complications. Platelet-activating factor (PAF) is secreted in massive amounts during AS, and a high plasma level is correlated with increased AS severity., Objective: To assess the effect of ABT-491, a PAF-receptor antagonist and possible adjunct treatment, alone or in combination with epinephrine during AS., Methods: AS was induced by intravenous injection of 1 mg ovalbumin into ovalbumin-sensitized rats. Rats were then randomly assigned to 5 groups (n = 10 per group): SHAM (vehicle only), SHOCK (no treatment), ABT (ABT-491 1 mg/kg), EPI (epinephrine 5 µg as a bolus then 10 µg kg -1  min -1 by continuous infusion, followed by a reducing protocol) and EPI-ABT (both treatments)., Results: Ovalbumin injection resulted in a severe decrease in mean arterial pressure, left ventricular inotropy (max dP/dt) and left ventricular shortening fraction (LVSF). All rats from the ABT group survived until the end of the experiment. ABT-491 prevented the LVSF decrease observed in the SHOCK group (at T15: ABT 50% ± 11% vs SHOCK 36% ± 9%, P = .01), significantly reduced the dose of epinephrine needed to treat anaphylactic shock (EPI-ABT 314 ± 67 µg/kg vs EPI 475 ± 69 µg/kg, P < .001) and reduced the time to restore basal MAP (ABT 23 ± 7 minutes vs EPI-ABT 13 ± 5 minutes, P < .01)., Conclusions and Clinical Relevance: AS was characterized by early cardiac dysfunction in our model. Treatment with ABT-491 allowed survival until the end of the experiment and reduced cardiac dysfunction. Use of the PAF-R antagonist had a synergistic effect with epinephrine and allowed a significant reduction in epinephrine consumption. Use of PAF-R antagonists during AS could reduce epinephrine-related complications and improve the treatment of epinephrine refractory cases., (© 2019 John Wiley & Sons Ltd.)

Atrial fibrillation is the most common cardiac arrhythmia in western society affecting more than 35 million individuals worldwide annually. It is a common postoperative complication and may also occur spontaneously during general and local anesthesia administration. Aging, diabetes mellitus, hypertension, and cardiovascular diseases including cardiomyopathies, congenital cardiac anomalies, heart failure, myocardial ischemia, pericarditis, previous cardiac surgery, vascular disease, and valvular heart disease are some correlated factors. Beyond age, increased incidence of atrial fibrillation has been correlated to autoimmune system activation as it is the underlying mechanism of persistent atrial fibrillation development. Current research supports an association between the complement system activation and lymphocyte-pro-inflammatory cytokines release with the cardiac conduction system and atrial fibrosis. The loss of CD28 antigen from CD4+ CD28+ T lymphocytes seems to play a major role in atrial fibrillation development and prognosis. Except atrial fibrillation, a variety of additional electrocardiographic changes, resembling those with digitalis intoxication may accompany anaphylaxis and particularly Kounis syndrome. Histamine is one well-known mediator in allergic and inflammatory conditions as physiologically regulates several cardiovascular and endothelial functions with arrhythmogenic potential. The increased oxidative stress, measured by the redox potentials of glutathione, has been correlated with atrial fibrillation incidence and prevalence. The use of antazoline, a first-generation antihistamine agent used for rapid conversion of recent-onset atrial fibrillation in patients with preserved left ventricular function and for rapid atrial fibrillation termination during accessory pathway ablation denotes that anaphylaxis-induced histamine production could be the cause of atrial fibrillation at least in some instances. The anaphylaxis diagnosis in anesthesia can be challenging owing to the absence of cutaneous manifestetions such as flushing, urticaria, or angioedema. Anticoagulation for stroke prevention, rate and rhythm control medications, invasive methods such as radiofrequency ablation or cryoablation of pulmonary veins as well surgical ablation constitute the treatment basis of atrial fibrillation. Understanding the underlying mechanisms of atrial fibrillation by cardiologists, anesthesiologists and surgeons, as well as potential treatments, to optimize care is of paramount importance.

Objective: Little is known regarding food anaphylaxis in infancy. We aimed to describe specificities of food anaphylaxis in infants (≤12 months) as compared to preschool children (1-6 years)., Methods: We conducted a retrospective study of all food anaphylaxis cases recorded by the Allergy Vigilance Network from 2002 to 2018, in preschool children focusing on infants., Results: Of 1951 food anaphylaxis reactions, 61 (3%) occurred in infants and 386 (20%) in preschool children. Two infants had two anaphylaxis reactions; thus, we analyzed data among 59 infants (male: 51%; mean age: 6 months [SD: 2.9]); 31% had a history of atopic dermatitis, 11% of previous food allergy. The main food allergens were cow's milk (59%), hen's egg (20%), wheat (7%) and peanut (3%) in infants as compared with peanut (27%) and cashew (23%) in preschool children. Anaphylaxis occurred in 28/61 (46%) cases at the first cow's milk intake after breastfeeding discontinuation. Clinical manifestations were mainly mucocutaneous (79%), gastrointestinal (49%), respiratory (48%) and cardiovascular (21%); 25% of infants received adrenaline. Hives, hypotension and neurologic symptoms were more likely to be reported in infants than in preschool children (P = .02; P = .004; P = .002, respectively). Antihistamines and corticosteroids were more often prescribed in preschool children than in infants (P = .005; P = .025, respectively)., Conclusion: Our study found that in infants presenting with their first food allergy, in a setting with a high rate of infant formula use, the most predominant trigger was cow's milk. As compared to older preschool children, hives, hypotonia and hypotension were more likely to be reported in infants. We believe that this represents a distinct food anaphylaxis phenotype that can further support developing the clinical anaphylaxis criteria in infants., (© 2019 John Wiley & Sons Ltd.)

Childhood allergy is common, and increasing. Many children are incorrectly labeled as having allergy or adverse drug reactions. This can pose a dilemma for anesthetists and lead to a change in practice or drug selection. We review the pathophysiology of hypersensitivity reactions and the implications for anesthesia of food allergy, atopy, and family history of allergy in children. The epidemiology of anaphylaxis is discussed. We discuss the common triggers of perioperative anaphylaxis in children and explore emerging triggers including chlorhexidine and sugammadex. Accurate data on pediatric perioperative anaphylaxis is limited worldwide, with marked geographic variation. This highlights the need for accurate local, district and/or nationwide incident reporting. The clinical features, diagnosis, and management of anaphylaxis under anesthesia are discussed. We review the process of expert allergy testing following a suspected case of anaphylaxis to guide future safe anesthesia administration. The preoperative consultation is an opportunity for referral for allergy testing to allow de-labeling. This has the potential for improved antibiotic stewardship and more effective treatment with first-line therapeutic agents., (© 2019 John Wiley & Sons Ltd.)

Background: Despite numerous efforts to describe the clinical manifestations and the epidemiology of perioperative hypersensitivity (POH), there remains room to increase awareness among anesthetists and immunologists/allergists., Objective: To report the findings of a 17-year survey of suspected POH in Antwerp, Belgium., Methods: We analyzed clinical and diagnostic data from 715 patients referred because of a suspected POH reaction, between January 1, 2001, and May 31, 2018. A total of 456 patients demonstrating a POH could be queried about subsequent anesthesia., Results: A total of 608 cases formed the final dataset; 208 had a non-life-threatening reaction and 400 a life-threatening reaction. In life-threatening reactions, hypotension was predominating. In the non-life-threatening reactions, 83.9% of the patients displayed cutaneous manifestations. In life-threatening reactions, intravenous adrenaline and fluids were administered in 75.7% and 31%, respectively, and 41.3% had their intervention abandoned. Mast cell activation (MCA) was mainly, but not exclusively, observed in severe grades but did not predict the mechanistic process nor the culprit. A cause was identified in 77.8% of severe and 48.6% of milder cases. Main culprits were neuromuscular blocking agents, latex, cefazolin, and dyes. A total of 156 cases had uneventful anesthesia, except 1 patient who was inadvertently re-exposed to hidden chlorhexidine., Conclusions: This study highlights that there is room for an improved acute management and an optimized diagnostic workup that should not be restricted to patients with severe reactions and/or showing MCA., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Systemic anaphylaxis is a life-threatening and allergic reaction that affects various organs. We previously reported that, in the stomach, gastric vasoconstriction occurring at the late phase (15-55 min after injection of ovalbumin antigen) was observed in anesthetized rats sensitized with ovalbumin. In addition, anaphylaxis enhances gastric motility and delays emptying. However, the role of extrinsic autonomic nervous system on antigen-induced gastric alterations was not known. Thus, using the same rat anaphylaxis model, we aimed to determine the changes in the efferent and afferent autonomic nerve activities in the stomach during anaphylactic hypotension. The findings showed that injection of ovalbumin antigen caused substantial systemic hypotension in all sensitized rats. The efferent gastric sympathetic nerve activity (ef-GSNA), but not the efferent vagal nerve activity, increased only at the early phase (1-10 min after injection of ovalbumin antigen) and showed baroreceptor reflex, as evidenced by a stimulatory response to sodium nitroprusside-induced hypotension. In general, excitation of ef-GSNA could induce pylorus sphincter contraction and gastric vasoconstriction. In the present study, we found that sympathectomy attenuated the anaphylaxis-induced decrease in gastric flux but not the increase in gastric vascular resistance. Thus, the increase in ef-GSNA may cause anaphylactic pylorus sphincter contraction but not anaphylactic gastric vasoconstriction. On the other hand, the afferent gastric vagal nerve activity, but not the afferent sympathetic nerve activity, increased during the early phase of anaphylactic hypotension. However, vagotomy produced no effects on the anaphylactic gastric dysfunction. In conclusion, the gastric sympathetic nerves partly modulate stomach function during systemic anaphylaxis.

Diagnosing and managing patients in shock is a challenge for the treating clinicians in acute medicine. Early diagnosis and treatment are crucial. Mortality of septic shock is between 40 % and 60 %, and that of the cardiogenic shock about 40 %. This article provides an overview of diagnostic approaches to the patient in shock, different aetiologies and treatment strategies, and it guides the clinician through the management from first contact until definite treatment., Competing Interests: Dr. Hempel gibt an, dass kein Interessenkonflikt besteht. Prof. Dr. Michels hat Honorare für Vorträge von folgenden Firmen erhalten: Pfizer, Novartis, Servier, Zoll, Getinge und Orion Pharma. Er gibt an, dass hierdurch kein Konflikt mit der vorliegenden Arbeit besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Perioperative hypersensitivity reactions (POH) constitute a clinical and diagnostic challenge, a consequence of heterogeneous clinical presentations, and multiple underlying pathomechanisms. POH do not necessarily involve an allergen-specific immune response with cross-linking of specific immunoglobulin E (sIgE) antibodies on mast cells and basophils. POH can also result from alternative specific and non-specific effector cell activation/degranulation such as complement-derived anaphylatoxins and off-target occupancy of mast cell, basophil, or both surface receptors. Moreover, POH and anaphylaxis can occur independent from mast cell and basophil degranulation. The manifestations of POH primarily affect the cardiovascular, respiratory, and integumentary systems. POH present within the context of surgical or procedural pathology and the effects of surgical and anaesthetic techniques on pre-existing physiological reserve. The majority of cases of appropriately-treated intraoperative anaphylaxis can be considered a compensated cardiovascular anaphylaxis. With increasing severity of anaphylaxis, maldistribution and hypovolaemia lead to reduced venous return and circulatory failure. Treatment with a combination of epinephrine and i.v. fluid is critical for successful resuscitation, although the excessive use of epinephrine without adequate volume expansion may be deleterious. Neural control of the airways is important in the pathophysiology of bronchospasm. Anticholinergic drug premedication is beneficial in patients with hyperreactive airways. Pulmonary oedema can result from a combination of pulmonary capillary hypertension, incompetence of the alveolocapillary membrane, or both. Angioedema can be distinguished mechanistically into histaminergic and non-histaminergic (e.g. bradykinin-mediated). An understanding of the molecular mechanisms and pathophysiology of POH are essential for the immediate management and subsequent investigation of these cases., (Copyright © 2019 British Journal of Anaesthesia. All rights reserved.)

Purpose of Review: The following article provides an overview of food-dependent exercise-induced anaphylaxis (FD-EIAn). The review focuses on the epidemiology, pathophysiology, and clinical findings of FD-EIAn and details current practice in terms of the investigation, management, and treatment options available., Recent Findings: The management of FD-EIAn has not changed significantly over the last few years and still requires careful investigation by an experienced clinician to ensure that the correct diagnosis is made and appropriate treatment is given. Although new therapies such as synthetic prostaglandin E1 analogs and IgE monoclonal antibodies have been trialed as treatment options for FD-EIAn, the mainstay of treatment remains the graded reintroduction to exercise in a supervised setting., Summary: FD-EIAn is a rare but serious condition that can have a significant impact on patients' lives. This review aims to discuss new relevant research into this field to help guide clinicians in managing this condition.

Background: The rate of true vaccine allergy is unknown. Children with potential IgE-mediated adverse events following immunization (AEFI) should undergo allergy investigation that may include skin testing or challenge. Previous protocols tend to be highly conservative and often suggest invasive testing for all, a practice not evidence based, technically difficult, and unpleasant in children. It has more recently been suggested that skin testing may be restricted to those with allergic-like events within the first hour and those with a history of anaphylaxis., Objective: We aimed to describe the outcome of vaccine skin testing and challenge in children referred to a tertiary pediatric hospital with a potential IgE-mediated AEFI. The secondary aim was to identify any significant risk factors for vaccine allergy., Methods: A retrospective review of all children (<18 years) who underwent vaccine skin testing (skin prick testing or intradermal testing [IDT]) or challenge over a 5-year period (May 1, 2011, to April 30, 2016) at the Royal Children's Hospital Melbourne is presented., Results: There were 95 admissions in 73 children. Eight percent (6 of 73) of children had confirmed vaccine allergy (positive skin testing or challenge to the index vaccination). Two had positive IDT to a suspect vaccine but challenge negative to an alternative brand vaccine. Two had negative IDT but subsequent positive challenge and two had immediate urticaria on challenge without prior skin testing. All children in the positive group either had index reaction within 15 minutes of vaccination or had history consistent with anaphylaxis., Conclusions: The vast majority of children (92%) presenting with a potential IgE-mediated AEFI are able to tolerate challenge to a suspect vaccine without reaction. We present our investigation protocol recommending skin testing in all children with anaphylaxis and challenge with a suspect vaccine if negative testing or previous nonanaphylactic potential IgE-mediated AEFI., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: The advantages of clinical simulation used in medical education include the acquisition of clinical skills in a controlled setting, promoting a multidisciplinary approach to patient care, and a high degree of learner satisfaction., Objective: We aimed to identify knowledge gaps among Internal Medicine residents and students in the diagnosis and treatment of anaphylaxis and angiotensin-converting enzyme (ACE)-inhibitor-induced angioedema through their participation in a simulation course., Methods: We conducted a cohort study involving clinical simulations with a high-fidelity, patient-simulator. The cases (antibiotic-induced anaphylaxis and ACE-inhibitor-induced angioedema) were standardized and algorithmic. Participants completed a pre- and post- simulation knowledge assessment and course evaluation. A follow-up knowledge survey was sent out 6 to 12 months after the course completion., Results: Twelve groups comprising 45 medical students and residents completed the anaphylaxis course. All groups diagnosed anaphylaxis after more than 2-organ-system involvement had manifested, and half of the groups made the diagnosis after the patient-simulator was in anaphylactic shock. Half gave an incorrect dose of epinephrine, and most of the participants were inexperienced in epinephrine auto-injector (EAI) administration. Eight groups comprising 27 participants completed the ACE-inhibitor-angioedema course. Six of the groups correctly diagnosed the patient-simulator, but multiple incorrect treatments were given, and only 1 group successfully intubated the patient-simulator. Knowledge improved immediately after the simulation, and knowledge specific to EAI treatment seemed to be retained long-term. All participants agreed that the simulation was practical to their education., Conclusion: Clinical simulation improves knowledge on the diagnosis and treatment of anaphylaxis and ACE-inhibitor-induced angioedema. We advocate that clinical simulation be incorporated at institutions with appropriate capabilities., (Copyright © 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Mast cell activation syndrome (MCAS) is a rare condition defined by a severe systemic reaction to mast cell (MC)-derived mediators. Most cases present with clinical signs of anaphylaxis, and some have an underlying IgE-dependent allergy. A primary MC disease (mastocytosis) may also be detected. Severe recurrent MCAS episodes requiring intensive care or even resuscitation are typically found in patients who suffer from both mastocytosis and allergy against certain triggers, such as hymenoptera venom components. A less severe form and a local form of MC activation (MCA) also exist. For these patients, diagnostic criteria are lacking. Moreover, a number of different, unrelated, conditions with overlapping symptoms may be confused with MCAS. As a result, many patients believe that they are suffering from MCAS but have in fact a less severe form of MCA or another underlying disease. In the current article, we review the potential differential diagnoses of MCA and MCAS and discuss available diagnostic criteria and diagnostic tools. These criteria and assays may be useful in daily practice and help avoid unnecessary referrals and unjustified fears in patients., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Infant anaphylaxis is an emerging risk, with food allergy the most common cause. Although the presentation of anaphylaxis involves the same systems as in older children and adults, there are real-world challenges to identifying symptoms of an allergic emergency in nonverbal children, as well as implementing optimal treatment. Recognition of anaphylaxis in infants can be challenging because allergic symptoms and certain normal infant behaviors may overlap. Intramuscular epinephrine is the treatment of choice for infants, as it is for older children and adults, and an epinephrine autoinjector approved by the Food and Drug Administration is now available for infants weighing between 7.5 and 15 kg. A panel of experts sought to develop guiding principles for the recognition, diagnosis, and management of anaphylaxis in infants, and provide a framework for the development of new guidelines and future research. Accordingly, anaphylaxis emergency action planning for infants was addressed by the panel. In considering formation of future infant anaphylaxis guidelines, health care providers should be aware of the needs to improve the recognition, diagnosis, and management of infants with anaphylaxis. Future research should identify and validate clinical criteria for the diagnosis of anaphylaxis in infants, as well as risk factors for the most severe reactions., (Copyright © 2019. Published by Elsevier Inc.)

A 52-year-old patient was scheduled for a cystoscopy. Anesthesia was induced by intravenous injection of fentanyl and propofol. After administration of atracurium, he became bradycardic and suffered a cardiac arrest. Despite prolonged cardiopulmonary resuscitation, the patient could not be revived. Electrolytes and hemoglobin levels were normal, and a transthoracic echocardiogram showed no signs of pericardial effusions or of any left ventricular contraction. The postmortem found no pathology. However, mast cell tryptase was raised significantly, indicating fatal anaphylaxis. Having presented no classic clinical signs, this case is a reminder that rapid cardiovascular collapse can be the sole clinical feature of anaphylaxis.

Adrenaline autoinjectors (AAIs) improve outcomes and reduce fatalities in patients with anaphylaxis, but many patients neither carry them nor know how to use them. Practitioner training in evidence-based strategies designed to increase patient adherence could improve the likelihood of AAI adherence and increase confidence among practitioners to initiate discussions about practical and perceptual barriers to AAI adherence. This article reports the development of a new practitioner training intervention, grounded in health psychology theory and evidence designed for practitioners in contact with patients with anaphylaxis to encourage adherence to AAIs. Potential implications for the design, implementation, and evaluation of future practitioner training in strategies they can use to encourage anaphylaxis patients' AAI adherence are discussed. Although designed for those working with anaphylaxis patients, this step-by-step process to encouraging adherence could be adapted for practitioners working with patients living with other long-term conditions.

Introduction: Exercise-induced anaphylaxis (EIA) denotes a range of disorders where anaphylaxis occurs in relation to physical exercise. Typical symptoms include flushing, pruritus, urticaria, angioedema, respiratory symptoms, gastrointestinal symptoms, hypotension, and collapse during or after exercise. The far best described entity within EIA is food-dependent exercise-induced anaphylaxis (FDEIA), where symptoms only occur in combination with food intake. Frequency and predictability of symptoms vary, and some patients experience symptoms only if exercise is accompanied by other co-factors Areas covered: In the present review, we aimed to provide an overview of EIA, diagnostic workup, causes, management and discuss areas in need of further research. Expert opinion: Though rare, EIA is an entity that all allergists and practicing physicians should recognize. The pathophysiological and immunological mechanisms of EIA are largely unknown. Management is centered upon avoidance of eliciting factors, where emergency plans are individualized, except a mandatory prescription of an adrenaline auto-injector.

Introduction: Although pediatric emergencies commonly occur in the outpatient setting, studies show that primary care providers often rely on hospitals or the emergency medical system to evaluate the distressed patient. This simulation-based curriculum addresses pediatric emergencies encountered by primary care providers. The cases were facilitated by faculty at an annual conference on urgent pediatric problems., Methods: Three cases are included in this curriculum: asthma, anaphylaxis, and seizure. Each features a brief narrative description of the case, learning objectives, instructor notes, an example of the ideal flow of the scenario, and anticipated management mistakes. Also provided are tools on optimizing the simulation environment, teamwork and communication, and the debrief. Educational materials are included in the respective medical pathologies. The simulations can be run using a high- or low-fidelity mannequin., Results: The simulations were carried out annually for 4 years with over 100 providers. Participants overall felt the curriculum was relevant to their practice in the realms of medical management and patient-provider communication., Discussion: These simulation cases train primary care providers to recognize a decompensating patient, activate the emergency response system, and initiate appropriate treatment for acutely ill pediatric patients with asthma, anaphylaxis, or seizure. The cases also reinforce teamwork and communication skills with the intention of improving overall readiness in the office. The simulations have been found to be effective learning tools at the University of Washington, which continues to train outpatient providers in emergency response annually using this curriculum., Competing Interests: None to report.