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Background: Fatal anaphylaxis is very rare, with an incidence ranging from 0.5 to 1 deaths per million person-years. Objective: Based on a systematic review, we aimed to explain differences in the reported incidence of fatal anaphylaxis based on the methodological and demographic factors addressed in the various studies. Methods: We searched PubMed/MEDLINE, EMBASE, and the Web of Science for relevant retrospective and prospective cohort studies and registry studies that had assessed the anaphylaxis mortality rate for the population of a country or for an administrative region. The research strategy was based on combining the term “anaphylaxis” with “death”, “study design”, and “main outcomes” (incidence). Results: A total of 46 studies met the study criteria and included 16,541 deaths. The range of the anaphylaxis mortality rate for all causes of anaphylaxis was 0.002-2.51 deaths per million person-years. Fatal anaphylaxis due to food (range 0.002-0.29) was rarer than deaths due to drugs (range 0.004-0.56) or Hymenoptera venom (range 0.02-0.61). The frequency of deaths due to anaphylaxis by drugs increased during the study period (IRR per year, 1.02; 95%CI, 1.00-1.04). We detected considerable heterogeneity in almost all of the meta-analyses carried out. Conclusion: The incidence of fatal anaphylaxis is very low and differs according to the various subgroups analyzed. The studies were very heterogeneous. Fatal anaphylaxis due to food seems to be less common than fatal anaphylaxis due to drugs or Hymenoptera venom.

Postmortem tryptase is a commonly used biochemical test to aid in the diagnosis of fatal anaphylaxis, which is currently recommended to be sampled from peripheral (femoral) veins because of a research showing comparatively elevated levels from central blood sources. Previous studies have used nonstandardized or nondocumented sampling methods; however, more recent research demonstrates that tryptase levels may vary depending on the sampling method. This study used the recommended sampling method of aspirating the femoral vein after clamping and compared in a pairwise comparison with aspiration of central venous and arterial blood sources (inferior vena cava and aorta) in 2 groups of 25 nonanaphylactic deaths. We found no statistically significant differences in postmortem tryptase between central and femoral vein blood; however, sporadic outliers in central blood (particularly aortic blood reaching levels above documented cutoffs for fatal anaphylaxis) were observed. Our findings provide evidence for the existing recommendations that femoral vein blood remains the preferred sample for postmortem tryptase over central blood.

Hymenoptera stings are accountable for significant morbidity and deterioration in health-related quality of life due to the allergic reactions they cause, the most severe of which can culminate in fatal anaphylaxis. The availability of high quality venom extracts for use in the diagnosis and treatment of insect venom allergy has improved the prognosis and the health-related quality of life of venom-allergic patients. All over the world subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy with an early, sustained and long-term efficacy. Even though the type of insect responsible for allergic reactions may be different from Europe and US and therefore also the type of extract, nevertheless indications and contraindications are quite similar, as well as treatment protocols and treatment duration. However, neither the efficacy nor the safety of the treatment are optimal, especially with regard to bee venom immunotherapy, and so there is considerable room for further improvement in these important areas. This review presents the current practice of venom immunotherapy in Europe and United States discussed at the EAACI (European Academy of Allergy and Clinical Immunology) Allergy School on Insect Venom held in Groningen in April 2019.

Background The pigeon tick Argas reflexus is a temporary parasite of pigeons. It bites during night hours and lies briefly on its prey, as long as it takes the blood meal. When pigeons are not accessible, ticks look for other hosts, invading nearby flats and biting humans. Case presentation We present the case of a woman aged 46 years who experienced severe anaphylaxis during the night which required emergency medical treatment, tracheal intubation and hospitalization in intensive care unit. Kounis syndrome was documented by transient ST depression and elevation of troponin. The allergological work up ruled out hypersensitivity to drugs, latex and foods containing alpha-gal, which is a cause of anaphylaxis. Basal serum tryptase was in normal range (8.63 ng/ml). When questioned about the presence of ticks, the patient brought into view various specimens of ticks that were recognized by an entomologist as Argas reflexus. Conclusions An in vitro diagnosis of allergy to Argas reflexus is currently not feasible because, though the major allergen Arg r 1 has been isolated, allergen extracts are not commercially available. Therefore, the diagnosis of anaphylaxis from Argas reflexus, when other causes of anaphylaxis are excluded, must rely only on history and clinical findings, as well as on the presence of pigeons and/or pigeon ticks in the immediate domestic environment.

Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one-quarter of sting-induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long-term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta-blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline-directed antihypertensive treatment. The absence of urticaria/angioedema during sting-induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom-allergic patients. Measurement of platelet-activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use.

A 44-year-old healthy farmer, was stung by a scorpion on his right hand while preparing soil for planting in the Caatinga area (a large area in the north-east of Brazil characterized by semiarid scrub forest), in the Catarina Municipality countryside, Ceará State, Brazil. According to the reports of carers and family members, the patient initially reported mild pain at the site of the sting, but within a few minutes he developed malaise, pruritus in the body and throat, edema in the nostrils, and a dry mouth which led to looking for water to drink. It rapidlyevolved into sphincter, urinary and fecal release, salivation and a convulsive episode with loss of the senses. He was dead on arrival at Catarina Municipality Hospital emergency department.The necroscopic report indicated suffocation due to glottal edema and acute lung edema as the “cause of death”. The animal which caused the accident was under a rock that the patient was manipulating at the time of the incident, and has been identified by experts as Jaguajir rochae (Borelli, 1910) scorpion species, formerly synonymized Rhopalurus rochae. This is the first report of a fatality due to an allergic reaction to the venom of this species. This leads to the possibility that deaths caused by stings from other scorpion species may be due to anaphylaxis, whose symptoms in some situations may be confused with severe envenomation. KEY WORDS: Jaguajir rochae; scorpionism; anaphylaxis; allergy

Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one-quarter of sting-induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long-term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta-blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline-directed antihypertensive treatment. The absence of urticaria/angioedema during sting-induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom-allergic patients. Measurement of platelet-activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use.

SUMMARY Severe allergic reactions (anaphylaxis) are unpredictable, and initial signs of what could be fatal anaphylaxis can be mild Adrenaline (epinephrine) remains the first-line drug of choice for the acute management of anaphylaxis and should be administered early There are no contraindications to intramuscular adrenaline in the treatment of anaphylaxis Correct positioning of the patient is vital as death can occur within minutes if a patient stands, walks or sits up suddenly. Position the patient correctly first and then promptly administer intramuscular adrenaline Updated guidelines by the Australasian Society of Clinical Immunology and Allergy now recommend that the 0.15 mg adrenaline injector device may be prescribed for infants and children weighing 7.5–10 kg. The recommendation to use the 0.3 mg adrenaline injector device for those over 20 kg remains unchanged The adrenaline doses in Australian Prescriber’s anaphylaxis wallchart remain valid

The safety and efficacy of ondansetron has led to its wider clinical use and this could increase unusual serious adverse events. Therefore, we emphasize the need for cautious use of ondansetron and beware and prepare for unusual adverse events.

Mastocytosis is a neoplasm characterized by an accumulation of mast cells in various organs and increased risk for severe anaphylaxis in patients with concomitant allergies. Coronavirus disease 2019 (COVID-19) is a pandemic that is associated with a relatively high rate of severe lung disease and mortality. The mortality is particularly high in those with certain comorbidities and increases with age. Recently, several companies have developed an effective vaccination against COVID-19. Although the reported frequency of severe side effects is low, there is an emerging discussion about the safety of COVID-19 vaccination in patients with severe allergies and mastocytosis. However, even in these patients, severe adverse reactions are rare. We therefore recommend the broad use of COVID-19 vaccination in patients with mastocytosis on a global basis. The only well-established exception is a known or suspected allergy against a constituent of the vaccine. Safety measures, including premedication and postvaccination observation, should be considered in all patients with mastocytosis, depending on the individual personal risk and overall situation in each case. The current article provides a summary of published data, observations, and expert opinion that form the basis of these recommendations.

Background: anaphylaxis is a severe, systemic hypersensitivity reaction that can be potentially life-threatening. Anaphylaxis during oral food challenge is not uncommon and can usually be effectively managed with intramuscular adrenaline as first line treatment. Although very rare, fatal anaphylaxis during in-hospital food challenge has been reported. Objective: we describe our experience of cases of refractory anaphylaxis at in-hospital challenge and propose a framework for escalation of treatment in such cases using intravenous infusion of adrenaline which has been adopted for widespread use elsewhere. Methods: we present four patients who all experienced severe life-threatening anaphylaxis, refractory to intramuscular adrenaline treatment, during supervised oral food challenges. Patient data were collected from contemporaneous notes, and patient consent was obtained. Results: in all four cases, the anaphylaxis reactions were amenable to treatment with low-dose intravenous adrenaline, with no reported adverse effects. Conclusion and clinical relevance: these cases demonstrate the need for clinicians undertaking higher risk allergen challenges to be able to manage cases of severe anaphylaxis refractory to intramuscular adrenaline, and to consider a framework for managing these reactions. While peripheral intravenous adrenaline infusions should always be initiated only in conjunction with expert input, the protocol suggested is simple enough to be undertaken within the hospital environment while more experienced support is obtained.

Fluorescein Angiography (FA) is a technique that employs the designated camera for Fundus photography incorporating excitation and barrier filters. FA also requires fluorescein dye that is injected intravenously, which might cause adverse effects ranging from nausea, vomiting to even fatal anaphylaxis. Currently, no other fast and non-invasive technique exists that can generate FA without coupling with Fundus photography. To eradicate the need for an invasive FA extraction procedure, we introduce an Attention-based Generative network that can synthesize Fluorescein Angiography from Fundus images. The proposed gan incorporates multiple attention based skip connections in generators and comprises novel residual blocks for both generators and discriminators. It utilizes reconstruction, feature-matching, and perceptual loss along with adversarial training to produces realistic Angiograms that is hard for experts to distinguish from real ones. Our experiments confirm that the proposed architecture surpasses recent state-of-the-art generative networks for fundus-to-angio translation task., 8 pages, 4 figures, 2 tables

Furosemide is a potent diuretic, with structural similarity to sulphonamide antibiotics. Its relative safety profile is one of the reasons to account for its widespread use. We report a rare case of fatal anaphylaxis with intravenous furosemide administered in our critical care settings for pulmonary edema. Chemical similarity of furosemide with sulphonamide antibiotics shares the possibility of similar allergic side effects. Thus, a more careful clinical use of furosemide, especially if administered intravenous should be kept in mind to avoid such catastrophic events.

Anaphylaxis is a serious systemic allergic reaction that is rapid in onset and may cause death. Despite numerous national and international guidelines and consensus statements, common misconceptions still persist in terms of diagnosis and appropriate management, both among healthcare professionals and patient/carers. We address some of these misconceptions and highlight the optimal approach for patients who experience potentially life-threatening allergic reactions.

Anaphylaxis is a severe and potentially life-threatening allergic reaction. There are numerous potential causes, with food allergy being the leading cause in children and the focus of this review. Most reactions involve an IgE-mediated mechanism, although non-IgE-mediated and nonimmunologic reactions can occur. Various cofactors to be discussed can place certain individuals at an increased risk of severe or fatal anaphylaxis. The clinical manifestations of anaphylaxis are broad and may involve multiple body systems. Diagnosis of food-related anaphylaxis is primarily based on signs and symptoms and supported, wherever possible, by identification and confirmation of a culprit food allergen. First-line treatment of anaphylaxis is intramuscular administration of epinephrine. Long-term management is generally focused on strict allergen avoidance and more recently on food desensitization using immunotherapy. This review provides an overview of anaphylaxis with a specific focus on food allergy.

Epinephrine is the only effective treatment for anaphylaxis but studies routinely show underutilization. This is especially troubling given the fact that fatal anaphylaxis has been associated with delayed administration of epinephrine. Many potential barriers exist to the proper use of epinephrine during an anaphylactic reaction. This article will explore both patient-and physician-related factors, as well as misconceptions that all contribute to the underuse of epinephrine for the treatment of anaphylaxis.

BACKGROUND: Patients with indolent systemic mastocytosis (ISM) are at risk for severe anaphylactic reactions to yellow jacket (YJ) stings while demonstration of sensitization can be challenging because specific IgE (sIgE) levels are regularly below 0.35 kU(A)/L. The implication of missing YJ allergy is illustrated by a case of fatal anaphylaxis.OBJECTIVE: To explore the natural course of YJ venom allergy and the diagnostic accuracy and therapeutic consequence of YJ venom sIgE in patients with ISM.METHODS: All patients with ISM seen from 1981 to 2015 (n = 243) were evaluated on the number of YJ stings, reaction severity, and sensitivity and specificity of YJ venom sIgE. YJ venom allergic patients without mastocytosis served as control (n = 313).RESULTS: A total of 153 patients with ISM were stung during adult life. The first systemic reaction was more often severe in patients with ISM than in patients without mastocytosis (69.9% vs 22.0%) and reactions recurred in 40 of 41 re-stung patients with ISM. ISM reactors showed lower YJ venom sIgE levels than nonmastocytosis reactors (0.61 vs 4.83 kU(A)/L; P CONCLUSIONS: The high rate of severe reactions and the fatal case underscore the importance of adequate diagnostic sensitivity of sIgE in patients with ISM. The sensitivity of sIgE can be ameliorated by lowering the threshold to 0.17 kU(A)/L, retaining good specificity. We recommend sIgE screening in all patients with ISM and discussing immunotherapy when YJ venom sIgE exceeds 0.17 kU(A)/L.

Post-mortem investigation in cases of fatal anaphylaxis is required to provide clarifications on the presence of macroscopic pathological changes, histological features, and immunohistochemical positivity suggestive of the diagnosis, on biochemical evidence of anaphylaxis and on the presence of serological data indicative of the allergen responsible for the anaphylactic reaction. We describe the case of a 16-year-old boy with a medical history of allergic asthma, celiac disease, and known food-induced allergy for fish, fresh milk, peanuts, hazelnuts, walnuts, apples, kiwis, and peaches. Acute onset of dyspnea followed by cyanosis of the lips and respiratory failure was described immediately after having an ice cream sandwich. Unsuccessful rescues were immediately attempted with oral administration of betamethasone, intramuscular injection of adrenaline, and cardiopulmonary resuscitation. A complete post-mortem examination was performed. Serum dosage of mast cell beta-tryptase from femoral blood detecting serum values of 41.4 mg/l. Determination of specific IgE on cadaveric blood samples confirmed the anamnestic data related to sensitization for several food allergens, including cod parvalbumin, tropomyosin, brazil nut, omega-5-gliadin of foods derived from wheat and gluten. The cause of death was identified in a cardiorespiratory failure due to anaphylactic shock in a poly-allergic subject and anaphylaxis was ascribed to the wheat contained in the ice cream sandwich eaten immediately before the onset of respiratory symptoms. The need is to implement an interdisciplinary approach capable to ascertain the sensitivity and specificity of the diagnostic tests currently in use as well as to evaluate the possibility of introducing new biomarkers in practice.

Peanut allergy is one of the most common food allergies in children, with increasing prevalence over time. The dual-allergen exposure hypothesis now supports transcutaneous sensitization to peanut as a likely pathophysiologic mechanism for peanut allergy development. As a result, there is emerging evidence that early peanut introduction has a role in peanut allergy prevention. Current first-line diagnostic tests for peanut allergy have limited specificity, which may be enhanced with emerging tools such as component-resolved diagnostics. Although management of peanut allergy includes avoidance and carrying an epinephrine autoinjector, risk of fatal anaphylaxis is extremely low, and there is minimal risk related to cutaneous or inhalational exposure. Quality of life in children with peanut allergy requires significant focus. Moving forward, oral and epicutaneous immunotherapy are emerging and exciting tools that may have a role to play in desensitization to peanut.

Baseggio Conrado and colleagues note that, although hospital admissions for food induced anaphylaxis increased between 1998 and 2018, the case fatality rate for confirmed food anaphylaxis decreased over this 20 year period, from 0.7% to 0.19%.1 Improved survival might result from better management, but misclassification of deaths should also be considered, especially as fatalities are rare. Having evaluated deaths for the United Kingdom Fatal Anaphylaxis Registry (UKFAR), we raise the …

Purpose of review The frequency of hospitalization for anaphylaxis has increased over the last 20 years across Europe, Australia, and North America, particularly, for food and medication triggers. Adolescents show the highest risk for morbidity and fatality from food-induced anaphylaxis, yet there is little high-quality evidence addressing the reasons for this disproportionate vulnerability. Recent findings Recent data seem to suggest a possible increasing burden of food-induced anaphylaxis among adolescents. Trends in anaphylaxis mortality are stable in North America and the United Kingdom, but not in Australia where the incidence of fatal anaphylaxis has recently doubled. The age distribution of fatal anaphylaxis varies according to the nature of the culprit trigger, with data suggesting an age-related predisposition to fatal food anaphylaxis in adolescents and young adults. Adolescence represents a critical phase of transition when rapid and substantial physical, emotional, and social changes occur. Therefore, adolescents show challenges in self-management that are different from other age groups, contributing to a higher risk of poor anaphylaxis outcomes. Summary The purpose of this review is to summarize recent data on epidemiology and elicitors of anaphylaxis in adolescents and to address currently known barriers and potential facilitators to self-management of anaphylaxis in this vulnerable age group.

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.

The incidence of fatal anaphylaxis is significantly higher among young people aged 15–25 compared with other age groups. Hospital admission or fatal outcome following anaphylaxis often results from failure to adhere to an agreed anaphylaxis action plan (AAP). The main barriers for adherence include lack of confidence to recognise symptoms of severe reaction, lack of confidence and skills to correctly use an adrenaline auto-injector (AAI), and not having the AAI available when needed. We describe the development of a smart phone application (app) to increase young peoples’ adherence to AAP. The development of the app was informed by information from a literature review to identify factors enhancing and impeding young peoples’ adherence to their AAP, combined with data from consultations with intended users and clinicians working with young people at risk of anaphylaxis regarding their needs and expectations with regard to the content and technical features of the app. The design process was underpinned by the novel Behavioural Intervention Technologies model. This ensured that the apps’ content is evidence based, complies with current guidelines, and responds to users’ needs and preferences in relation to content and technical characteristics. ‘Anaphylaxis’ app is the first smart phone app that comprises a comprehensive personalised AAP. Since its launch in February 2013, it has been downloaded by approximately 16 000 users worldwide. Further research is required to demonstrate its effectiveness in improving self-management of anaphylactic risk in young people.

Venomous insect stings are a cause of morbidity and mortality worldwide. The sting reactions are unpredictable and vary among individuals. A case of fatal insect sting in an elderly female is presented to discuss the associated challenges during necropsy.

An allergy is a hypersensitive reaction of the body when it comes into contact with a substance that is in fact harmless .An allergy is certain cause occurs suddenly and is predictable . The hypersensitive response comes from the natural immune system and ranges from a slightly uncomfortable feeling to a fatal anaphylaxis. Light allergies are part everyday life . Allergic rhinitis , hay fever characterized by runny nose ,red eyes and itchiness. Food allergy causes vomiting, watery stools, rashes, substances that causes allergy often are proteins in food such as milk, wheat, beef, eggs, and so on the allergy, such as blood tests, skin tests etc. Ocular allergy includes several clinically different conditions that can be considered as hypersensitivity disorders of ocular surface. Ocular allergy symptoms are often but not always associated with other allergic manifestation mostly rhinitisSometimes the eyes can react to other allergens that don’t necessarily come in direct contact with the eye, such as specific type of food material.

BACKGROUND: Anaphylaxis hospitalisations are increasing in many countries, in particular for medication and food triggers in young children. Food-related anaphylaxis remains an uncommon cause of death, but a significant proportion of these are preventable. AIM: To review published epidemiological data relating to food-induced anaphylaxis and potential risk factors of fatal and/or near-fatal anaphylaxis cases, in order to provide strategies to reduce the risk of severe adverse outcomes in food anaphylaxis. METHODS: We identified 32 published studies available in MEDLINE (1966-2017), EMBASE (1980-2017), CINAHL (1982-2017), using known terms and synonyms suggested by librarians and allergy specialists. RESULTS: Young adults with a history of asthma, previously known food allergy particularly to peanut/tree nuts are at higher risk of fatal anaphylaxis reactions. In some countries, cow's milk and seafood/fish are also becoming common triggers of fatal reactions. Delayed adrenaline injection is associated with fatal outcomes, but timely adrenaline alone may be insufficient. There is still a lack of evidence regarding the real impact of these risk factors and co-factors (medications and/or alcohol consumption, physical activities, and mast cell disorders). CONCLUSIONS: General strategies should include optimization of the classification and coding for anaphylaxis (new ICD 11 anaphylaxis codes), dissemination of international recommendations on the treatment of anaphylaxis, improvement of the prevention in food and catering areas and, dissemination of specific policies for allergic children in schools. Implementation of these strategies will involve national and international support for ongoing local efforts in relationship with networks of centres of excellence to provide personalized management (which might include immunotherapy) for the most at-risk patients. This article is protected by copyright. All rights reserved.

International audience; AbstractAnaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction. The difficulty of coding anaphylaxis fatalities under the World Health Organization (WHO) International Classification of Diseases (ICD) system is recognized as an important reason for under-notification of anaphylaxis deaths. On current death certificates, a limited number of ICD codes are valid as underlying causes of death, and death certificates do not include the word anaphylaxis per se. In this review, we provide evidences supporting the need for changes in WHO mortality coding rules and call for addition of anaphylaxis as an underlying cause of death on international death certificates. This publication will be included in support of a formal request to the WHO as a formal request for this move taking the 11th ICD revision.