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Background: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests., Methods: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins., Results: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06)., Conclusions: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objective: The aim of this study was to estimate the incidence of anaphylaxis in pregnancy and describe the management and outcomes in the UK., Design: A population-based descriptive study using the UK Obstetric Surveillance System (UKOSS)., Setting: All consultant-led maternity units in the UK., Population: All pregnant women who had anaphylaxis between 1 October 2012 and 30 September 2015. Anaphylaxis was defined as a severe, life-threatening generalised or systemic hypersensitivity reaction., Methods: Prospective case notification using UKOSS., Main Outcome Measures: Maternal mortality, severe maternal morbidity, neonatal mortality and severe neonatal morbidity., Results: There were 37 confirmed cases of anaphylaxis in pregnancy, giving an estimated incidence of 1.6 (95% CI: 1.1-2.2) per 100 000 maternities. Four cases of anaphylaxis were in women with known penicillin allergies: two received co-amoxiclav and two cephalosporins. Twelve women had anaphylaxis following prophylactic use of antibiotics at the time of a caesarean delivery. Prophylactic use of antibiotics for Group B streptococcal infection accounted for anaphylaxis in one woman. Two women died (5%), 14 (38%) women were admitted to intensive care and seven women (19%) had one or more additional severe maternal morbidities, which included three haemorrhagic events, two cardiac arrests, one thrombotic event and one pneumonia. No infants died; however, in those infants whose mother had anaphylaxis before delivery (n = 18) there were seven (41%) neonatal intensive care unit admissions, three preterm births and one baby was cooled for neonatal encephalopathy., Conclusions: Anaphylaxis is a rare severe complication of pregnancy and frequently the result of a reaction to antibiotic administration. This study highlights the seriousness of the outcomes of this condition for the mother. The low incidence is reassuring given the large proportion of the pregnant population that receive prophylactic antibiotics during delivery., Tweetable Abstract: Anaphylaxis is a rare severe complication of pregnancy and frequently the result of a reaction to antibiotic administration., (© 2017 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Background: In 2012, an analysis of the Brazilian mortality database demonstrated undernotification of anaphylaxis deaths due, at least in part, to difficult coding under the International Classification of Diseases (ICD)-10. This work triggered a cascade of strategic international actions supported by the Joint Allergy Academies and the ICD World Health Organization (WHO) representatives to update the classifications of allergic disorders for the ICD-11 revision. These efforts have resulted in the construction of the new 'Allergic and hypersensitivity conditions' section under the 'Disorders of the Immune system' chapter., Objective: To analyze the capacity of the new ICD-11 revision to capture anaphylaxis deaths., Methods: We re-estimated the anaphylaxis deaths that occurred in Brazil during the period 2008 to 2010, utilizing this new framework and the database of the Brazilian mortality information system that had initially been extracted in May 2011. However, in 2016, a manual review of each of the 3638 records was performed., Results: We identified 639 anaphylaxis deaths, of which 95% were classified as 'definitive anaphylaxis deaths'. In contrast to the 2012 published data, we found a higher number of cases; moreover, all 606 definitive anaphylaxis deaths would be considered as underlying causes of death utilizing the ICD-11 revision., Conclusion: This study is the first example of how the new 'Allergic and hypersensitivity conditions' section of the forthcoming ICD-11 can improve the quality of official vital statistics data and the visibility of an important public health concern. This research will facilitate comprehensive, comparable population-based epidemiologic data collection on anaphylaxis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Monitoring after complete resolution of anaphylactic reactions is recommended. The aim of this study was to define the occurrence of biphasic - and clinically important biphasic - anaphylactic reactions, the number of transfers to intensive care units (ICU) because of anaphylaxis, and the number of deaths within 10 days of presentation to the emergency department (ED)., Methods: Clinical records of patients visiting the ED of a tertiary care hospital were analysed retrospectively. Hospital databases, direct contact with patients and caregivers, and the Internet were used to obtain mortality rates., Results: Of 259 557 ED presentations from February 2001 through to August 2013, 1334 (0.51%) episodes of allergic reactions were detected, and 532 (0.20%) episodes in 495 patients fulfilled the definition of anaphylaxis. In 227 (44.8%) episodes, the length of hospital stay was ≥8 h (median 22 h, IQR 16-24). There were 507 uniphasic and 25 (4.5%) biphasic anaphylactic reactions. Twelve (2.3%) were clinically important, including 2 (0.36%) that occurred during hospital stay, one of whom (0.19%) was transferred to ICU for shock. No risk factors for biphasic reactions could be found. Eight patients were lost to follow-up. There were no deaths during the 10-day follow-up., Conclusion: Biphasic anaphylactic reactions, especially clinically important ones, occurred rarely, and no mortality was found, whether the monitoring was for ≥8 h or for <8 h. Our study could motivate physicians to consider discharging patients after complete resolution of an anaphylactic reaction and to dispense with prolonged monitoring., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Undernotification is well recognized as a key challenge to the study of anaphylaxis mortality, but it is seldom mentioned that one of its reasons is the difficult coding of the condition under the tenth revision of the international classification of diseases (ICD-10), given that there are no anaphylaxis-specific ICD-10, which are considered valid for coding underlying causes-of-death, and that official mortality statistics consider exclusively the underlying and disregard the contributing causes-of-death data recorded on death certificates. Brazilian mortality data were used as a case study to call attention to the inadequacy of the ICD-10 for the measurement of anaphylaxis deaths., Methods: Underlying and contributing causes-of-death data were used to estimate the rates of anaphylaxis deaths in the country over the years 2008-2010., Results: Of 498 anaphylaxis deaths were found, of which 75% were classified as 'definite' and 25% as 'possible anaphylaxis deaths'. The average national rate for these years was 0.87 per million per year. None of these deaths would have been found had we exclusively considered information from the underlying cause-of-death field., Conclusion/recommendations: The study of anaphylaxis mortality using secondary data requires the use of information derived from the underlying as well as from the contributing causes-of-death fields. Coding definitions should be standardized with a view of enabling trend analyses and international comparisons. The ICD-11 revision is a unique opportunity to improve the coding system so as to facilitate epidemiological studies of anaphylaxis mortality. Educational interventions targeted at improving the quality of death certificate completion are urgently needed., (© 2012 John Wiley & Sons A/S.)

Controversy exists about the safety of the parenteral iron dextran products, Dexferrum and INFeD, which have been associated with rare, serious anaphylactic-type reactions. In the United States, their product labels carry boxed warnings of this adverse event; some have called for the withdrawal from marketing of the higher molecular weight Dexferrum. Between 2002 and 2007, sales of Dexferrum, INFeD, and iron gluconate Ferrlecit declined 32.5%, 21%, and 4.8%, respectively, while sales of iron sucrose Venofer increased 160%. Voluntary reports submitted to the Food and Drug Administration show anaphylactic reactions and symptoms for the four parenteral iron products. Because of underreporting, possible differential reporting, absence of iron dextran brand names, and incomplete use (denominator) data, incidence rates and relative risk estimates cannot be calculated. U.S. death certificate data show that for most years from 1979 through 2006, no more than 3 deaths per year were coded to "adverse events in therapeutic use of iron preparations;" brand names were not consistently recorded. Emergency department data show small numbers of visits for treatment of allergic reactions with intravenous iron preparations. The data presented herein show that allergic reactions are possible with all four parenteral iron products, and it is difficult to determine which product has the largest risk based on sales data, voluntarily submitted adverse event reports, death certificates, ED visits, and observational studies performed to date. To help differentiate risk among the parenteral iron products, the brand name of the product always should be provided on medical records, death certificates, and adverse drug reaction reports., (Published 2010 Wiley-Liss, Inc.)

Background: Previous US population-based epidemiologic studies of anaphylactic deaths have been limited by small populations and/or few deaths. The objective of this study was to determine the 10-year incidence of death from anaphylaxis in Florida and its descriptive epidemiology., Methods: Patients who died from anaphylaxis from 1996 to 2005 were identified from ICD-9 and ICD-10 codes on death certificates statewide. Age, race and gender-specific anaphylactic death rates were calculated., Results: There were 89 deaths among Florida residents. The individuals with autopsy confirmed diagnoses, and those with clinical diagnoses only, did not differ with regard to race, anaphylactic triggers or the clinical variables of lung and heart disease. Annual death rate for anaphylaxis in Florida was 5.02/10 000 000. The relative risk of death from anaphylaxis was 14.09 for individuals > or =65 years old (P = 0.0000002) and 6.38 for individuals 35-64 years old (P = 0.0019) compared with those who were 5-14 years of age. Deaths among Florida residents that occurred in emergency rooms or outpatient settings were 2.11 times as likely to be anaphylactic deaths than deaths that occurred in inpatient settings (P = 0.0026). The ratios of anaphylactic deaths to total deaths in March and April and in July and August were greater than the ratios for the other bimonthly periods (P = 0.02)., Conclusion: Death from anaphylaxis in Florida was more likely to occur in older individuals, in an emergency department, and in the months of March and April and July and August.

Severe anaphylaxis is a systemic reaction affecting two or more organs or systems and is due to the release of active mediators from mast cells and basophils. A four-grade classification routinely places 'severe' anaphylaxis in grades 3 and 4 (death could be graded as grade 5). Studies are underway to determine the prevalence of severe and lethal anaphylaxis in different populations and the relative frequencies of food, drug, latex and Hymenoptera anaphylaxis. These studies will also analyse the risk arising from the lack of preventive measures applied in schools (personalized management protocols) and from the insufficient use of self-injected adrenalin. Allergy-related conditions may account for 0.2-1% of emergency consultations. Severe anaphylaxis affects 1-3 per 10 000 people, but for the United States and Australia figures are even higher. It is estimated to cause death in 0.65-2% of patients, i.e. 1-3 per million people. An increased prevalence has been revealed by monitoring hospitalized populations by reference to the international classification of disease (ICD) codes. The relative frequency of aetiological factors of allergy (food, drugs, insects and latex) varies in different studies. Food, drug and Hymenoptera allergies are potentially lethal. The risk of food-mediated anaphylaxis can be assessed from the number of personalized management protocols in French schools: 0.065%. Another means of assessment may be the rate of adrenalin prescriptions. However, an overestimation of the anaphylaxis risk may result from this method (0.95% of Canadian children). Data from the literature leads to several possibilities. First, a definition of severe anaphylaxis should be agreed. Secondly, prospective, multicentre enquiries, using ICD codes, should be implemented. Moreover, the high number of anaphylaxis cases for which the aetiology is not identified, and the variation in aetiology in the published series, indicate that a closer cooperation between emergency specialists and allergists is essential.

To date, there are no population-based epidemiologic studies providing information about the prevalence of food-induced anaphylaxis. However, statistics from the United Kingdom demonstrated an increase of anaphylaxis from 5.6 cases per 100,000 hospital discharges in 1991-92 to 10.2 cases in 1994-95. The increase for the subcategory of food-induced anaphylaxis was above the overall increase in anaphylaxis. In the UK register of fatal anaphylactic reactions, all food-induced fatalities have been accompanied by respiratory problems with respiratory arrest. Atopic individuals with bronchial asthma and prior allergic reactions to the same food are at a particularly high risk. Not only peanuts, seafood and milk can induce severe, potentially lethal, anaphylaxis, but indeed a wide spectrum of foods, according to the different patterns of food sensitivity in different countries. Foods with "hidden" allergens and meals at restaurants are particularly dangerous for patients with food allergies. Similarly, schools, public places and restaurants are the major places of risk. However, the main factor contributing to a fatal outcome is the fact that the victims did not carry their emergency kit with adrenaline (epinephrine) with them. Therefore, we suggest that the pharmaceutical industry should reintroduce an adrenaline inhaler that is more effective, especially in asthmatic reactions.

We measured mast-cell tryptase in postmortem blood from 22 heroin addicts dying suddenly after injection. In 32%, the concentration of tryptase was elevated (> or = 10 micrograms/l), and the mean value of tryptase was significantly different from a control group dying from known, nonimmunologic causes (P < 0.05). The increased tryptase concentrations indicate that death was preceded by systemic mast-cell degranulation. All victims of drug deaths had morphine in blood, most below 0.2 microgram/ml. In 71% of the victims of drug-related deaths with tryptase values > or = 10 micrograms/l, the intermediate degradation product, 6-monoacetyl-morphine, was not found in blood, whereas this was the case in only two victims with values below that cutoff point. This indicates that those with high tryptase concentrations survived longer than those with lower values. No correlation was found between the IgE levels and tryptase in either group, supporting the hypothesis that tryptase release was not mediated by an allergic reaction. The well-known property of opiates to stimulate unspecifically the liberation of histamine and other constituents of mast-cell granules offers one explanation of our observations. The results suggest that many heroin fatalities are caused by an anaphylactoid reaction.

During a 21-year period in Denmark a total of 26 deaths were caused by wasp or bee stings (according to the National Health Service). The deaths might be classified, with some overlapping, as caused by either anaphylactic/anaphylactoid shocks (between 65% and 80%), suffocation after stings in the airways (about 15%) or preexisting diseases, especially arteriosclerotic heart disease (approx. 20%). Characteristically, in most persons with shock reactions unconsciousness and death occurred very shortly after the sting (within 45 min), while the interval between sting and death was longer (30 min to a couple of hours) when death was caused by suffocation. In more than 21 of the 26 cases it seemed reasonable to assume that insect allergy might have contributed to the fatal outcome. Six of these cases had a previous history of abnormal reactions to insect venom, thus only a small group would have benefited from the prophylactic effect of hyposensitisation. There was no known previous history of reactions to insect stings in the other cases, but it is likely that more than six persons had had severe reactions to insect stings on other occasions. Presumably many deaths where insect stings have been involved--through not verified as causal--are classified as inexplicable or accidental, thus the real number of deaths caused by wasp or bee stings could be substantially greater. Consequently hyposensitisation after severe insect sting reactions of verified allergic genesis can still be advised.