Increase in anaphylaxis-related hospitalizations but no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992-2012.

BACKGROUND: The incidence of anaphylaxis might be increasing. Data for fatal anaphylaxis are limited because of the rarity of this outcome. OBJECTIVE: We sought to document trends in anaphylaxis admissions and fatalities by age, sex, and cause in England and Wales over a 20-year period. METHODS: We extracted data from national databases that record hospital admissions and fatalities caused by anaphylaxis in England and Wales (1992-2012) and crosschecked fatalities against a prospective fatal anaphylaxis registry. We examined time trends and age distribution for fatal anaphylaxis caused by food, drugs, and insect stings. RESULTS: Hospital admissions from all-cause anaphylaxis increased by 615% over the time period studied, but annual fatality rates remained stable at 0.047 cases (95% CI, 0.042-0.052 cases) per 100,000 population. Admission and fatality rates for drug- and insect sting-induced anaphylaxis were highest in the group aged 60 years and older. In contrast, admissions because of food-triggered anaphylaxis were most common in young people, with a marked peak in the incidence of fatal food reactions during the second and third decades of life. These findings are not explained by age-related differences in rates of hospitalization. CONCLUSIONS: Hospitalizations for anaphylaxis increased between 1992 and 2012, but the incidence of fatal anaphylaxis did not. This might be due to increasing awareness of the diagnosis, shifting patterns of behavior in patients and health care providers, or both. The age distribution of fatal anaphylaxis varies significantly according to the nature of the eliciting agent, which suggests a specific vulnerability to severe outcomes from food-induced allergic reactions in the second and third decades.

Factors predicting anaphylaxis to peanuts and tree nuts in patients referred to a specialist center.

BACKGROUND: Although acute allergic reactions after ingestion of peanuts and tree nuts are common, fatalities are rare. Other than patients with coexisting asthma, it is currently not possible to predict which patients are most likely to develop severe reactions. OBJECTIVE: The aim of this study was to determine which clinical and laboratory parameters best predict the likelihood of severe allergic reactions. METHODS: From 1992 to 2004, we collected detailed information on the clinical severity and allergy test results of 1094 patients with peanut and tree nut allergy attending a regional allergy center. In a subgroup of 122 patients, sera were assayed for activity of enzymes involved in the catabolism of bradykinin. RESULTS: Severe pharyngeal edema was 3.8 (2.1-6.9) times more common in patients with severe rhinitis and 2.6 (1.8-3.7) more common after ingestion of tree nuts compared with peanuts. Patients with serum angiotensin-converting enzyme concentrations <37.0 mmol/L had a 9.6 (1.6-57)-fold risk of severe pharyngeal edema. Life-threatening bronchospasm was most likely in patients with severe asthma (relative risk, 6.8 [4.1-11.3]) and less so in patients with milder asthma (2.7 [1.7-4.0]). Altered levels of consciousness were more likely in patients with severe eczema (3.1 [1.1-8.4]). CONCLUSION: Severity of coexisting atopic diseases predicted which patients attending a tertiary referral clinic were most likely to develop life-threatening allergic reactions to peanuts and tree nuts. Patients with the lowest serum angiotensin-converting enzyme concentrations were more likely to develop life-threatening pharyngeal edema, suggesting that this complication may be partly mediated by bradykinin.

When should self-injectible epinephrine be prescribed for food allergy and when should it be used?

PURPOSE OF REVIEW: To explore why epinephrine autoinjectors have failed to prevent fatal food anaphylaxis and how this problem might be solved. RECENT FINDINGS: Autoinjectors cannot save lives when they are used too late, misused, not carried, or when an inadequate dose is absorbed; food allergy-induced asthma may not respond when asthma management is suboptimal. New markers for severe reactions have been published. SUMMARY: The fallibility of autoinjectors means that in the management of food allergy, their provision must take second place to accurate identification of the trigger foods, optimal avoidance, and optimal treatment of other medical conditions that make reactions more dangerous.

Emergency treatment of anaphylactic reactions--guidelines for healthcare providers.

*The UK incidence of anaphylactic reactions is increasing. *Patients who have an anaphylactic reaction have life-threatening airway and, or breathing and, or circulation problems usually associated with skin or mucosal changes. *Patients having an anaphylactic reaction should be treated using the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach. *Anaphylactic reactions are not easy to study with randomised controlled trials. There are, however, systematic reviews of the available evidence and a wealth of clinical experience to help formulate guidelines. *The exact treatment will depend on the patient's location, the equipment and drugs available, and the skills of those treating the anaphylactic reaction. *Early treatment with intramuscular adrenaline is the treatment of choice for patients having an anaphylactic reaction. *Despite previous guidelines, there is still confusion about the indications, dose and route of adrenaline. *Intravenous adrenaline must only be used in certain specialist settings and only by those skilled and experienced in its use. *All those who are suspected of having had an anaphylactic reaction should be referred to a specialist in allergy. *Individuals who are at high risk of an anaphylactic reaction should carry an adrenaline auto-injector and receive training and support in its use. *There is a need for further research about the diagnosis, treatment and prevention of anaphylactic reactions.

IgE-mediated food allergy diagnosis: Current status and new perspectives.

In June 2005, the work of the EU Integrated Project EuroPrevall was started. EuroPrevall is the largest research project on food allergy ever performed in Europe. Major aims of the project are to generate for the first time reliable data on the prevalence of food allergies across Europe and on the natural course of food allergy development in infants. Improvement of in vitro diagnosis of food allergies is another important aim of the project. The present review summarizes current knowledge about the clinical presentation of food allergy and critically reviews available diagnostic tools at the beginning of the project period. A major problem in diagnosis is a relatively poor 'clinical specificity', i. e. both positive skin tests and in vitro tests for specific IgE are frequent in sensitized subjects without food allergy symptoms. So far, no in vitro test reliably predicts clinical food allergy. EuroPrevall aims at improving the predictive value of such tests by proceeding from diagnosis based on allergen extracts to purified allergen molecules, taking into account the affinity of the IgE-allergen interaction, and evaluating the potential of biological in vitro tests such as histamine release tests or basophil activation tests including assays performed with permanently growing cell lines.

Anaphylaxis: can we tell who is at risk of a fatal reaction?

PURPOSE OF REVIEW: Anaphylaxis is frightening and patients commonly fear their next reaction will be fatal. This review looks at the characteristics of fatal reactions to find if a fatal recurrence is predictable. RECENT FINDINGS: Most publications on fatal anaphylaxis are case reports that do not help predict risks. Most epidemiological studies focus on non-fatal reactions. The UK fatal anaphylaxis register demonstrates that over two-thirds of those dying from sting reactions and over four-fifths dying from drug anaphylaxis had no previous indication of their allergy, whereas those dying from food allergy had usually had previous reactions but these were typically not severe. Recent reports of anaphylaxis epidemiology based on diagnostic coding or attendance for treatment may be biased by differences in health service resource utilization according to the cause and course of the reaction. SUMMARY: Most fatal anaphylactic reactions are unpredictable. The appropriate management after recovery from a severe reaction may be protective against a fatal recurrence. An accurate identification of the cause and effective avoidance is a crucial part of this management, together with effective treatment of asthma for those with food allergy, immunotherapy for sting allergy, the avoidance of drugs that potentiate anaphylaxis, and effective training in self-treatment.

Fatal anaphylaxis in the UK, 1992-2001.

Each year in the UK, around nine deaths are attributed to anaphylaxis to pharmaceuticals, six to food and four to stings. I have identified 214 deaths associated with anaphylaxis, and have sufficient information for 196 to determine that 88 deaths were due to shock, 96 to asphyxia. Five deaths followed epinephrine overdose, seven were complicated by disseminated intravascular coagulation. There will have been other unrecognized fatal antibiotic and asthmatic food reactions. For foods, peak age was 17-27 with a female and atopic predominance; the first arrest was commonly from asthma 25-35 minutes after the implicated food. For stings, peak age was 45-70 with male and non-atopic predominance; death was commonly from shock 10-15 minutes after the sting. A majority of deaths from pharmaceuticals in hospital took 5 minutes or less from dose to arrest; peak age was 60-75. Maximum time for any cause from trigger to first arrest was 6 hours. The danger of epinephrine overdose and its limitations in reversing anaphylaxis must be recognized. The patient should remain supine with legs raised throughout sting and other shock reactions. Prevention of fatal food reactions will depend on avoidance and optimal daily control of asthma.

IgE sensitization to the nonspecific lipid-transfer protein Ara h 9 and peanut-associated bronchospasm.

Allergen component analysis is now available in many laboratories. The aim of this study was to examine the possible association between peanut allergen IgE components and severity of clinical reactions in patients with a history of peanut allergy. Data and sera collected from 192 patients within the Manchester Allergy Research Database and Serum Bank were used in this retrospective study. Sensitization to peanut specific IgE and Ara h 1, 2, 3, and 8 peanut IgE components, as measured by fluoroenzyme immunoassay, was not associated with anaphylaxis. In contrast, sensitization to the lipid-transfer protein Ara h 9 was significantly more prevalent in patients with peanut-associated bronchospasm (26% versus 9% of patients), even after adjusting for potential confounding effects of age, gender, and severity of concomitant chronic atopic diseases. Patients who were sensitized to Ara h 9 were more likely to have ingested rather than just have had skin contact with peanut and have a more rapid onset of symptoms. These results are consistent with observations that sensitization to heat and protease resistant lipid-transfer protein components of hazelnut, grains, and fruit is predictive of anaphylaxis.

The purification and characterisation of allergenic hazelnut seed proteins.

A lipid transfer protein (LTP, Cor a 8) together with the 11S (Cor a 9) and 7S seed storage globulins (Cor a 11) are major food allergens present in hazelnut. Methods are described for their purification and characterisation using in-gel tryptic digestion mass spectrometry to confirm their identities and circular dichroism and Fourier-transform infrared spectroscopies to demonstrate that they are authentically folded. Preliminary immunochemical studies have also confirmed that the purified preparations retain their immunological properties in terms of immunoglobulin E binding, determined by immunoblotting using serum from hazelnut allergic patients. These preparations form a basis for development of improved methods of diagnosis of food allergy based on the concept of component-resolved diagnosis.