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Fatal anaphylaxis

Fatal anaphylaxis
Author:
S Allan Bock, MD
Section Editor:
John M Kelso, MD
Deputy Editor:
Anna M Feldweg, MD
Literature review current through: Nov 2022. | This topic last updated: May 28, 2021.

INTRODUCTION — Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. It has been estimated to be fatal in 0.7 to 2 percent of cases [1,2]. In humans, fatal anaphylaxis is difficult to study because it is rare, unpredictable, and often unwitnessed. In addition, there may be few postmortem findings and laboratory tests may be negative.

This topic will review the incidence, etiologies, epidemiology, clinical characteristics, possible risk factors, and postmortem diagnosis of fatal anaphylaxis as they pertain to these fundamental questions. The diagnosis and management of anaphylaxis in adults is presented separately [3]. (See "Anaphylaxis: Emergency treatment" and "Pathophysiology of anaphylaxis".)

INCIDENCE — The annual incidence of fatal anaphylaxis is not known precisely, although available estimates are less than one per million in the population [4-13]:

A study of anaphylaxis deaths in the United States found annual rates of 0.21 to 0.76 per million [5].

Centralized registries of fatal anaphylactic reactions from all causes have been established in the United Kingdom, France, and some other countries [6,7]. In the United Kingdom, one case of fatal anaphylaxis per three million individuals yearly (approximately 20 deaths a year) has been reported [8].

A 2016 study from Australia found that rates of fatal anaphylaxis increased from 0.054 to 0.099 per million individuals from 1997 to 2013 [9].

A study from New Zealand estimated the rate to be approximately one per million [10].

Studies have drawn conflicting conclusions about whether the incidence of fatal anaphylaxis is changing over time [6,9,11,14-17]. The largest study available, from a French database, concluded that anaphylaxis deaths in that country were decreasing at a rate of 2 percent per year [12]. Another study found that drug-induced anaphylaxis was increasing in several countries, while anaphylaxis from other causes was stable [18].

Studies of fatal anaphylaxis caused by food-allergic reactions specifically are discussed separately. (See "Food-induced anaphylaxis", section on 'Fatal reactions'.)

Case fatality rate — Case fatality rates in the United States for patients treated for anaphylaxis (from all causes) either in the emergency department or hospital were estimated using three national databases and found to be between 0.25 and 0.33 percent, representing 63 to 99 deaths annually [5]. Thus, the prognosis for patients diagnosed and treated in these settings is relatively favorable. Mortality rates were highest in older male adults and lowest in children.

Possible underdiagnosis — Fatal anaphylaxis may be underdiagnosed because of the absence of specific findings at autopsy and lack of definitive diagnostic tests [19-21]. Examples of situations in which anaphylaxis is likely overlooked as the cause of death include the following [6]:

Asthmatic patients (especially children and adolescents) with concomitant food allergy may suffer food-induced anaphylaxis with prominent respiratory symptoms and be misdiagnosed as having a fatal asthma attack. It is therefore important to remind all patients with food allergy and asthma to think about what food they might have eaten when they have the abrupt onset of asthma without a clear trigger. This may be especially important when the asthma episode does not respond to the individual's usual treatment in the usual manner.

Older adults with chronic pulmonary disease may die at home from antibiotic-induced anaphylaxis and be misdiagnosed as a cardiac or respiratory arrest due to either the chronic condition or the recent infection.

Unrecognized insect stings may cause collapse and sudden death and be misdiagnosed as cardiovascular events, particularly if anaphylaxis involved myocardial ischemia or an arrhythmia. The cardiovascular aspects of anaphylaxis are reviewed separately. (See "Pathophysiology of anaphylaxis", section on 'Cardiovascular system'.)

ETIOLOGIES AND AT-RISK GROUPS — Fatal anaphylaxis can occur following a variety of triggers, although the most common culprits are medications, insect stings, and foods [12]. Approximately one-half of all anaphylactic fatalities each year in the United Kingdom register were attributable to medications or agents administered during medical procedures (such as contrast media) [6]. Reactions to foods and insect venoms each accounted for nearly one-quarter of the total cases, with other causes accounting for the remaining cases.

Medications — Beta-lactam antibiotics (ie, penicillins and cephalosporins) appear to cause more fatalities than other drugs [8,18,22]. Multiple other agents have been implicated in smaller numbers of cases, including the following [6,10,22-26]:

Radiocontrast agents

Neuromuscular blockers and anesthetics

Allergen immunotherapy

Other antibiotics

Adults are more often affected by medication-induced anaphylaxis, compared with children or adolescents [9,17,27].

Foods — Peanuts and tree nuts account for the majority of food-induced fatalities [6,28-31]. Cow's milk and seafood are also leading causes of severe and fatal reactions [32]. A variety of other foods have been implicated less commonly. At least two cases of fatal food-induced, exercise-associated anaphylaxis have been reported, although exercise or exertion is likely an unrecognized cofactor in other food-induced deaths [33,34]. (See "Clinical manifestations of food allergy: An overview".)

Adolescents and young adults are the most frequent victims of fatal food-induced anaphylaxis [8,17,30]. The following were observed in the United Kingdom register over a 10-year period [8]:

Fatal cow's milk reactions affected mostly children (median age was 8 years).

Fatal peanut reactions affected mostly young adults (median age was 21 years).

Fatal tree nut reactions affected mostly adults (median age was 27 years).

The reasons for the higher rate of food-induced deaths in adolescents and young adults are not clear. Risk-taking behaviors related to cognitive and emotional development are likely contributing factors. In an internet-based anonymous survey of 176 adolescents and young adults with food allergy, more than one-half reported purposefully ingesting a potentially unsafe food, and 17 percent reported both eating foods that "may contain" allergens and not consistently carrying epinephrine [35].

The one reported case of fatal anaphylaxis due to a food challenge occurred in a young child receiving baked milk [36]. (See "Oral food challenges for diagnosis and management of food allergies".)

Insect stings — Stings of Hymenoptera species (yellow jacket, honey bee, wasp, hornet, and imported fire ants) are one of the three leading causes of fatal anaphylaxis in the United States and United Kingdom [37-41]. Adults make up the majority of victims in venom-induced fatal anaphylaxis, with a peak incidence in patients 45 to 70 years [12,42]. Men are stung more often, perhaps due to higher rates of outdoor occupations. Older adults may be at increased risk for venom-induced death as well [41]. (See "Bee, yellow jacket, wasp, and other Hymenoptera stings: Reaction types and acute management" and "Stings of imported fire ants: Clinical manifestations, diagnosis, and treatment".)

Other causes — Other reported causes of fatal anaphylaxis include latex, rupture of a hydatid cyst, infestation with the parasite Taenia solium, dental impression material, and the herbal preparation Houttuynia cordata [6,43-47]. In some cases, no cause can be identified and the etiology is designated idiopathic [8,48,49].

EPIDEMIOLOGY — Individuals of any age can develop anaphylaxis, and fatalities have been reported in infants as young as 5 months and in adults as old as 91 years [27,29]. Certain trends are detectable, however. Adolescents and young adults are at highest risk for fatal anaphylaxis from foods, middle-aged adults are the most frequent victims of venom-induced deaths, and older adults account for most cases of fatal medication-induced anaphylaxis.

Location — Case series reveal that fatal food reactions occur in the patient's home, the homes of friends, restaurants, work/office settings, and schools [6,28,29,31]. Most food-induced anaphylaxis is triggered by food that was not prepared by the patients themselves [6].

High-risk foods for patients with peanut and tree nut allergies include baked goods, candy, and desserts. Issues pertaining to food allergen exposure are reviewed in detail separately. (See "Management of food allergy: Avoidance" and "Food allergy in schools and camps".)

Fatal stings can be sustained outdoors or indoors. Although outdoor occupations are often cited as a possible explanation for the predominance of male victims, a 10-year United Kingdom registry reported that only 15 percent of stings occurred at work, while 32 percent occurred in the patient's yard and 39 percent occurred inside the home (including 5 percent in bed) [50].

Medication-induced fatal anaphylaxis often occurs in a medically-supervised setting:

Most reported fatal anaphylactic reactions to medications and contrast agents occur in the hospital setting, which may reflect the wider range of agents used in this environment, higher rates of intravenous administration, or patient-related factors [10,51]. General anesthesia was associated with more fatalities than other hospital procedures in one series [50]. Alternatively, it is possible that community cases are under-recognized and under-reported. (See 'Possible underdiagnosis' above.)

Fatal anaphylactic reactions to allergen immunotherapy occur approximately once per 2.5 million injections administered and account for three to four deaths per year in the United States [26]. These reactions are most prevalent in the 20 to 30 minutes immediately following administration, and most allergists require patients to wait this amount of time in the clinic after each set of injections [25]. Rare deaths still occur despite this precaution.

Sex — It is not clear if sex contributes to the risk for fatal anaphylaxis, although some trends have been noted. As examples, the sex ratio is approximately equal for food anaphylaxis overall. However, young boys are affected more by fatal cow's milk reactions, and adolescent girls are affected more by peanut reactions [8,28,50]. Fatalities from contrast media and insect stings appear to affect males more than females [52,53]. In a large French series of 1603 deaths, men had an increased risk [12].

Race — A variety of ethnicities have been represented in studies of anaphylaxis. However, there are not enough data to determine if racial differences in mortality exist.

Registries — Worldwide, anaphylaxis registries are being established to gather information about anaphylaxis from various causes, some of which are specific to fatal cases:

National Food Death Allergy Registry (an online registry of individuals who suffered fatal food-induced anaphylaxis in the United States)

A European database

UK Fatal Anaphylaxis Register (not available online)

Cross-Canada Anaphylaxis Registry (C-CARE) (maintained by the Allergy, Genes, and Environment Network)

Several other countries are also tracking anaphylaxis and anaphylaxis fatalities but have not established formal registries.

CLINICAL CHARACTERISTICS OF FATAL REACTIONS — Case reports and series have provided valuable information about the clinical characteristics of fatal anaphylactic reactions.

Previous reactions — Victims of fatal anaphylaxis may not be aware that they are allergic to the implicated allergen [54]. In one series of 25 fatalities, the history of a previous reaction could be elicited from the patient's relatives or medical records in just one-third of cases [27]. Even in patients with known past reactions, the severity of previous reactions cannot be relied upon to predict the severity of future reactions, a finding which has been noted in multiple series [6,28-31,42,48].

In fatal food anaphylaxis, most individuals did have previous reactions to the culprit food and were supposed to be avoiding it. In many cases, however, these reactions were so mild that it is unlikely that most clinicians would have advised the patient to carry an epinephrine autoinjector. It is possible that these patients represent an unfortunate minority whose initial severe reaction proved fatal. Perhaps other patients' symptoms escalated gradually, prompting them to seek medical evaluation and thus be better prepared for re-exposure. The frequency of these different patterns is not known.

In contrast, victims of venom- and medication-induced anaphylaxis often had no known history of a previous reaction. In many cases of venom anaphylaxis, the individual was stung in the past and did not have systemic symptoms [50]. Similarly, no history of previous reactions to the causative medication can be elicited in some drug-induced fatalities [6,50].

Timing — Less than 60 minutes elapses between allergen exposure and death in most cases of fatal anaphylaxis [8,30]. Most fatal reactions are uniphasic, present fulminantly, and progress rapidly, although a few follow a more protracted or biphasic course, typically over several hours [30,55,56].

An analysis of 202 fatalities over a 10-year period in the United Kingdom determined that the interval between exposure and the onset of symptoms varied with the type of allergen and route of exposure, as follows [6]:

Following medications, symptoms appeared after a mean of 5 minutes in hospitalized patients and after 10 to 20 minutes in ambulatory patients.

Following insect stings, symptoms appeared after a mean of 10 to 15 minutes.

Following foods, symptoms appeared after 25 to 35 minutes.

Allergen dose — It seems logical that the higher the allergen dose, the more rapid and severe the reaction, although patients may have very different threshold levels beyond which they will experience anaphylaxis.

Fatal food anaphylaxis has been reported in response to a wide range of allergen doses, from trace amounts to doses in excess of 100 grams. In keeping with the impression that nuts are especially potent allergens, one review found that the dose of nuts that was most frequently implicated in fatalities was approximately 1 gram, while the dose most often reported in fatal anaphylaxis from other foods was about 10 grams [8].

Most insect sting fatalities result from a single sting [50].

Most drug-induced fatalities occur in response to normal doses of the culprit medication [50].

MECHANISM OF DEATH — Respiratory arrest and/or shock with cardiovascular collapse are responsible for most fatalities [57,58]. The mechanism of death appears to be determined, at least in part, by the type of allergen. In a review of 56 cases of fatal anaphylaxis for which autopsy data were available, all food-induced reactions involved difficulty breathing, and respiratory arrest was the mechanism of death in 13 of 16 cases [51]. In contrast, shock without respiratory compromise was the presentation in most cases of venom- or medication-induced anaphylaxis [59]. This correlation between allergen type and mechanism of death has been noted in many studies and is discussed in greater detail separately. (See "Pathophysiology of anaphylaxis".)

In a very small number of cases, massive epinephrine overdose or disseminated intravascular coagulation appeared to be the immediate cause of death [50].

POSSIBLE RISK FACTORS — The most consistently noted risk factor for fatal anaphylaxis is concomitant asthma. Other possible risk factors include delayed or no administration of epinephrine, upright posture, and other cardiopulmonary diseases (table 1).

Asthma — Asthma may be the single most important risk factor for fatal food-induced anaphylaxis. In the 10-year United Kingdom series, all fatal food reactions occurred in patients taking daily medications for asthma [50]. Although guidelines state that all patients with daily symptoms should be treated with inhaled glucocorticoids, many were not taking these agents, and some were using short-acting beta-agonists excessively. In another series of 32 food-induced fatalities, all but one patient had asthma [28].

Asthma also appears to be common among victims of drug- and venom-induced anaphylaxis, although the correlation is not as strong as that for food [50].

It is not known if controlling asthma reduces the risk of death from anaphylaxis. Most series have not reported the status of the individual's asthma at the time of his/her death, but the study above implies that at least some patients have poorly-controlled symptoms [50]. In contrast, one study of 13 fatal or near-fatal food reactions reported that 12 patients had asthma that was well-controlled [30].

Delayed or no administration of epinephrine — Early administration of epinephrine appears to be critical for survival after severe anaphylaxis. A series of 13 fatal and near-fatal food-induced anaphylactic reactions in children and adolescents suggested that epinephrine is most effective when given in the initial 30 minutes of the reaction [30]. Epinephrine was administered within this time period in six of seven children who survived, whereas only two of six patients who died received the drug within the first hour.

Several series have found that only a minority of individuals with fatal anaphylaxis receive epinephrine promptly or at all [6,27,30]. A United Kingdom series of anaphylactic deaths occurring from 1992 to 1998 found that only 20 percent of patients were given epinephrine at any point in their treatment [6].

The number of food- and venom-allergic individuals who do not carry their prescribed self-injectable epinephrine is large and discouraging. Furthermore, many of those who do carry it are unable to self-administer it promptly and correctly in a panic situation because they have not been instructed in how to use the device or have not practiced with the trainer.

No response to epinephrine — Even when epinephrine is available and administered without delay, it is not always effective for a number of reasons (table 2) [60]. There are reports of anaphylaxis, typically during medical procedures, in which the victim succumbed despite receiving appropriate treatment, including prompt administration of epinephrine. Thus, both clinicians and patients should understand that the recommended management of anaphylaxis is not universally effective.

Other cardiopulmonary disease — Other cardiac or pulmonary conditions are identified in a significant proportion of middle- and older-aged patients who succumb to anaphylaxis from all causes [6,27,61]. In one study, 88 percent of victims had one or more comorbid conditions, including 11 of 25 with symptomatic ischemic heart disease, as well as others with heart failure, hypertensive heart disease, and chronic obstructive pulmonary disease [27]. Other series found lower rates of concomitant diseases, although cardiac and pulmonary conditions consistently predominated [10,27,51].

It is biologically plausible that these comorbid conditions directly contribute to the fatal outcome, as the heart and lungs are the primary shock organs in anaphylaxis and could be expected to fail more readily if compromised by pre-existing disease. It is also possible that patients with cardiac disease are at increased risk for adverse reactions to treatment (especially intravenous boluses of epinephrine) [62]. However, the precise interplay between cardiopulmonary diseases and anaphylaxis are unclear. (See "Pathophysiology of anaphylaxis".)

Upright posture during anaphylaxis — Pulseless electrical cardiac activity has been identified at the time of death in some subjects with anaphylaxis, which is believed to result from inadequate cardiac filling during severe hypotension and subsequent cardiac arrest [9,63,64]. The term "empty ventricle syndrome" has been applied to this phenomenon [65]. Patients, caregivers, clinicians, and "first responders" must understand the importance of placing the patient in the supine position with legs elevated if signs of hypotension are present during an allergic reaction. (See "Anaphylaxis: Emergency treatment".)

Conscious individuals with bronchospasm may resist being placed supine, as sitting upright may ease the sense of dyspnea. In this setting, providing oxygen and explaining the reason for lying down are important, at least until the cardiovascular status can be assessed. Individuals who are vomiting and also hypotensive should be placed on their side rather than supine.

Initial misdiagnosis — Anaphylaxis can be mistaken for a variety of other conditions, such as asthma exacerbation, panic attack, myocardial infarction, and choking. In some cases, valuable time is lost or inappropriate medications are given before the correct diagnosis is recognized [6,50].

Systemic mastocytosis — Patients with systemic mastocytosis may be at higher risk for fatal anaphylaxis, even in the absence of immunoglobulin E (IgE)-mediated allergy. In the United Kingdom register, 2 of 164 individuals had systemic mastocytosis [6]. One died following a bee sting and the other died during anesthesia. (See "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)

Other atopic conditions — Nearly all patients who died of anaphylaxis were known to have had one or more allergic conditions or were clearly atopic by retrospectively gathered history [50]. Venom- and medication-induced anaphylaxis, however, typically afflict nonatopic individuals.

Exacerbating factors — The severity of anaphylaxis is believed to be increased in some cases by concurrent medications, foods, alcohol, exercise, premenstrual state, or other cofactors. These cofactors have been noted in both nonfatal and fatal anaphylaxis.

Beta-blocking agents and angiotensin-converting enzyme inhibitors interfere with the pharmacologic treatment of and compensatory physiologic responses to anaphylaxis, respectively. The presence of these medications has been noted in some studies of venom-induced fatalities and experimental sting challenges [66,67]. Patients taking these drugs, however, are not clearly over-represented in the literature on fatal anaphylaxis, and the impact of these medications requires further study.

A variety of other medications, including aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, alcohol, and antiulcer therapies, have been implicated in worsening the severity of anaphylaxis [68]. These agents are occasionally reported as cofactors in fatal anaphylaxis [50].

POSTMORTEM DIAGNOSIS — The diagnosis of fatal anaphylaxis is determined by the clinical presentation and historical information. Autopsy findings and laboratory testing may support the clinical impression, although they are not necessary or sufficient, in isolation, to make the diagnosis. In cases of sudden death of uncertain cause, femoral venous blood can be collected and the serum can be separated and frozen for later analysis [51].

Serum tests — Blood collected during or shortly after the event may be analyzed retrospectively for the mast cell-derived mediator tryptase and for evidence of immunoglobulin E (IgE) to the suspect allergen.

Tryptase is a mediator released by mast cells upon activation and is relatively specific to this cell type, although basophils also make a small amount. Any elevation is consistent with anaphylaxis. Tryptase levels that are within normal limits do not exclude the diagnosis. Tryptase is seldom elevated in food-induced anaphylaxis. The use of postmortem tryptase levels in the evaluation of possible fatal anaphylaxis is reviewed in more detail separately. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis".)

Quantitative IgE immunoassays may be helpful in detecting the presence of allergen-specific IgE in the victim's serum as a means of confirming that the patient was allergic to the allergen in question. Serum IgE levels do not change substantively as a result of anaphylaxis. Positive tests for allergen-specific IgE suggest the presence of sensitization. Negative assays do not exclude sensitization. Serum tests for sensitization to allergens are reviewed separately. (See "Overview of in vitro allergy tests".)

In one retrospective review, there were 56 cases of fatal anaphylaxis in which autopsy information was available [51]. Of these, 21, 19, and 16 fatalities were due to medications, insect venoms, and food allergies, respectively. Laboratory test results were not available in most cases. However, in the 16 cases of fatal anaphylaxis (due to a variety of agents) in which tryptase levels were measured, elevations were found in 14. In a series of 25 selected cases of fatal anaphylaxis, serum total tryptase concentrations were elevated in 4 of 7 cases tested [27].

Autopsy findings — Many victims have no distinguishing gross pathologic features at autopsy, particularly if shock develops rapidly [10,27,51]. When present, however, findings include upper airway edema, mucus plugging and hyperinflation of the lungs, and cerebral edema [69].

In the series of 56 cases mentioned previously, all individuals collapsed after allergen exposure, and 23 had a documented asthmatic component [51]. Dermatologic signs and symptoms were uncommon. The following macroscopic findings were reported:

Laryngeal or pharyngeal edema (41 percent)

Hyperinflation of the lungs and/or mucus plugging (27 percent)

Cerebral edema, suggesting cerebral hypoxia (27 percent)

Petechial hemorrhages in the airway mucosa, suggesting asphyxiation (18 percent)

Cutaneous erythema or urticaria (5 percent)

In cases where anaphylaxis to food is suspected at the time of death, the pathologist can be asked to preserve some of the stomach contents for later analysis for suspected food allergens.

PREVENTION — The literature provides some insight into predicting which individuals are at greatest risk for fatal anaphylaxis. These individuals most often have allergy to foods, medications, or insect venoms, accompanied by one or more of the following characteristics:

Concomitant asthma, particularly patients with food allergy

Comorbid cardiovascular conditions, particularly older patients

Thus, clinicians should be mindful of classic patient profiles, such as young patients with food allergy and asthma or older patients with insect sting or medication allergies and cardiopulmonary diseases. Such high-risk patients should be supplied with and trained to use epinephrine autoinjectors. Clinicians should repeatedly reinforce important concepts in anaphylaxis preparedness (table 3). Careful attention to asthma control may reduce risk. (See "Prescribing epinephrine for anaphylaxis self-treatment".)

Prevention of anaphylactic deaths in patients that are not known to have an allergy is a public health issue that will need to be addressed by campaigns to improve public awareness of anaphylaxis and specific protocols for first responders [70]. Similar approaches have been applied to community management of myocardial infarction, stroke, and choking. Anaphylaxis is rare compared with these events, although it often afflicts otherwise healthy people in the prime of life and is generally responsive to proper treatment.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anaphylaxis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: Anaphylaxis symptoms and diagnosis (Beyond the Basics)" and "Patient education: Anaphylaxis treatment and prevention of recurrences (Beyond the Basics)")

SUMMARY

Anaphylaxis is rare, although estimates of incidence are probably lower than the true figures. Anaphylaxis is believed fatal in up to 2 percent of cases. (See 'Incidence' above.)

The most common causes of fatal anaphylaxis are foods, medications, and insect stings. (See 'Etiologies and at-risk groups' above.)

Adolescents and young adults are at highest risk for fatal anaphylaxis induced by foods. Middle-aged and older adults account for most fatalities from venom- and medication-induced reactions. There are no clear differences between sexes or among racial groups. (See 'Epidemiology' above.)

Most patients with food-induced deaths were aware of the allergy and were supposed to be avoiding the culprit food. However, many had experienced only minor past reactions. Some patients with venom and medication reactions had no recognized reactions in the past. (See 'Previous reactions' above.)

Fatal anaphylaxis typically results in death within 30 to 60 minutes. The amount of allergen is usually unremarkable (eg, variable amounts of food, one insect sting, a normal dose of medication). (See 'Timing' above and 'Allergen dose' above.)

Most fatal food-induced reactions involve difficulty breathing and culminate in respiratory arrest. In contrast, venom- or medication-induced anaphylaxis more often cause shock and cardiovascular collapse. (See 'Mechanism of death' above.)

Concomitant asthma is a significant risk factor for fatal anaphylaxis, particularly for adolescents with food allergy. Older victims of anaphylaxis (from all causes) often have underlying cardiopulmonary conditions. (See 'Possible risk factors' above.)

Characteristics of unsuccessful treatment include delayed or no administration of epinephrine, either due to initial misdiagnosis, failure to properly administer epinephrine, or unavailability of this drug. Maintaining the patient in an upright position after collapse can lead to pulseless electrical activity and cardiac arrest (empty ventricle syndrome). Occasionally, victims succumb despite receiving prompt and appropriate treatment. (See 'Possible risk factors' above.)

The diagnosis of fatal anaphylaxis is based upon clinical features and historical information, supported by laboratory and autopsy findings. Femoral venous blood can be collected and the serum separated and frozen for later assays of tryptase and allergen-specific immunoglobulin E (IgE). Autopsy findings may be minimal. (See 'Postmortem diagnosis' above.)

Fatal anaphylaxis is unpredictable, although certain patients are at higher risk, such as those with concomitant asthma or cardiopulmonary disease. Clinicians should optimize asthma control and repeatedly reinforce important issues regarding anaphylaxis preparedness (table 3). (See 'Prevention' above.)

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Topic 390 Version 18.0

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