Case fatality and population mortality associated with anaphylaxis in the United States

doi:10.1016/j.jaci.2013.10.029

Journal of Allergy and Clinical Immunology

Volume 133, Issue 4, April 2014, Pages 1075-1083

https://doi.org/10.1016/j.jaci.2013.10.029 Get rights and content

Background

Anaphylaxis is a serious allergic reaction that can cause death; however, the actual risk of death is unclear.

Objective

We sought to estimate the case fatality rate among hospitalizations or emergency department (ED) presentations for anaphylaxis and the mortality rate associated with anaphylaxis for the general population.

Methods

This was a population-based epidemiologic study using 3 national databases: the Nationwide Inpatient Sample (NIS; 1999-2009), the Nationwide Emergency Department Sample (NEDS; 2006-2009), and Multiple Cause of Death Data (MCDD; 1999-2009). Sources for these databases are hospital and ED discharge records and death certificates, respectively.

Results

Case fatality rates were between 0.25% and 0.33% among hospitalizations or ED presentations with anaphylaxis as the principal diagnosis (NIS+NEDS, 2006-2009). These rates represent 63 to 99 deaths per year in the United States, approximately 77% of which occurred in hospitalized patients. The rate of anaphylaxis-related hospitalizations increased from 21.0 to 25.1 per million population between 1999 and 2009 (annual percentage change, 2.23%; 95% CI, 1.52% to 2.94%), contrasting with a decreasing case fatality rate among hospitalizations (annual percentage change, −2.35%; 95% CI, −4.98% to 0.34%). Overall mortality rates ranged from 0.63 to 0.76 per million population (186-225 deaths per year, MCDD) and appeared stable in the last decade (annual percentage change, −0.31%; 95% CI, −1.54% to 0.93%).

Conclusion

From 2006 to 2009, the overwhelming majority of hospitalizations or ED presentations for anaphylaxis did not result in death, with an average case fatality rate of 0.3%. Anaphylaxis-related hospitalizations increased steadily in the last decade (1999-2009), but this increase was offset by the decreasing case fatality rate among those hospitalized; both inpatient and overall mortality rates associated with anaphylaxis appeared stable and were well under 1 per million population. Although anaphylactic reactions are potentially life-threatening, the probability of dying is actually very low. With the prevalence of anaphylaxis on the increase, practitioners need to stay vigilant and follow the treatment guidelines to further reduce anaphylaxis-related deaths.

Section snippets

Data sources

Three separate databases were used in this study: the Nationwide Inpatient Sample (NIS; 1999-2009), the Nationwide Emergency Department Sample (NEDS; 2006-2009), and Multiple Cause of Death Data (MCDD; 1999-2009).19, 20, 21 These databases are deidentified for public use and were protected through data use agreements.

Anaphylaxis-related hospitalizations and inpatient deaths (NIS)

Between 1999 and 2009, the annual number of anaphylaxis-related hospitalizations increased from 5681 to 7708 (Table I), which corresponds to an increase in hospitalization rates from 21.0 to 25.1 per million population (Fig 1), with an annual increase of approximately 2.23% (95% CI, 1.52% to 2.94%; P < .01). In contrast, the case fatality rate among hospitalizations for anaphylaxis appeared to be decreasing, with an annual change of −2.35% (95% CI, −4.98% to 0.34%; P = .09). Case fatality rates

Discussion

There are many aspects of an anaphylactic reaction that make it frightening to both patients and health care providers, including rapidity of onset and potential for fatality. Because the onset of symptoms can occur rapidly and outside the health care setting, patients who have had anaphylactic reactions need to remain vigilant to try to prevent re-exposure to the causative allergen. Sometimes avoidance is not possible because the patient cannot prevent the exposure (eg, insect sting), the

References (38)

H.A. Sampson et al.
Second symposium on the definition and management of anaphylaxis: summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium
J Allergy Clin Immunol
(2006)
S.G. Johansson et al.
Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003
J Allergy Clin Immunol
(2004)
F.E. Simons
Anaphylaxis
J Allergy Clin Immunol
(2010)
P. Lieberman et al.
Epidemiology of anaphylaxis: findings of the American College of Allergy, Asthma and Immunology Epidemiology of Anaphylaxis Working Group
Ann Allergy Asthma Immunol
(2006)
M.W. Yocum et al.
Epidemiology of anaphylaxis in Olmsted County: a population-based study
J Allergy Clin Immunol
(1999)
K. Bohlke et al.
Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization
J Allergy Clin Immunol
(2004)
R.Y. Lin et al.
Increasing anaphylaxis hospitalizations in the first 2 decades of life: New York State, 1990-2006
Ann Allergy Asthma Immunol
(2008)
R.Y. Lin et al.
Increasing hospitalizations due to angioedema in the United States
Ann Allergy Asthma Immunol
(2008)
P.L. Owens et al.
Emergency department care in the United States: a profile of national data sources
Ann Emerg Med
(2010)
M. Ben-Shoshan et al.
Anaphylaxis: past, present and future
Allergy
(2011)

H. Kim et al.

Anaphylaxis

Allergy Asthma Clin Immunol

(2011)

J.K. Lee et al.

Anaphylaxis: mechanisms and management

Clin Exp Allergy

(2011)

M.J. Matasar et al.

Epidemiology of anaphylaxis in the United States

Curr Allergy Asthma Rep

(2003)

D.A. Moneret-Vautrin et al.

Epidemiology of life-threatening and lethal anaphylaxis: a review

Allergy

(2005)

S.D. Dibs et al.

Anaphylaxis in children: a 5-year experience

Pediatrics

(1997)

M.R. Simon et al.

A population-based epidemiologic analysis of deaths from anaphylaxis in Florida

Allergy

(2008)

Z.D. Mulla et al.

Hospitalizations for anaphylaxis in Florida: epidemiologic analysis of a population-based dataset

Int Arch Allergy Immunol

(2007)

A.I. Neugut et al.

Anaphylaxis in the United States: an investigation into its epidemiology

Arch Intern Med

(2001)

Z.D. Mulla et al.

Perspectives on anaphylaxis epidemiology in the United States with new data and analyses

Curr Allergy Asthma Rep

(2011)

Cited by (183)

Anaphylactic deaths: A retrospective study of forensic autopsy cases from 2009 to 2019 in Shanghai, China
2024, Heliyon
Anaphylaxis is a rare but well-known cause of sudden unexpected death, although data from forensic autopsies in anaphylactic deaths are limited. Herein, a retrospective study of a series of allergic deaths from 2009 through 2019 in Shanghai, China, was conducted to investigate the demographic, medical, and forensic pathological characteristics of fatal anaphylaxis to improve medicolegal understanding on anaphylactic death. Sixty-two autopsy cases of anaphylactic death were registered in this study. Males dominated the cases (74.2%) against females (25.8%), with an average age of 38.8 years. Medications (98.4%), particularly antibiotics (72.6%), were the most frequent cause of anaphylaxis, and 44 cases (71.0%) occurred in clinics administered illegally by unlicensed clinicians. The anaphylactic symptoms began within a few minutes to less than 1 h in 53 cases, with dyspnea (56.5%) and sudden shock (46.8%) being the most common clinical signs. Thirty cases (48.4%) of anaphylaxis resulted in death within 1 h. Laryngeal edema and multiple tissue eosinophil infiltration (85.5%) were the most prevalent autopsy findings, followed by pulmonary edema and congestion (24.2%), which were considered to be non-specific but suggestive. The comorbidities were mainly cardiovascular disease (33.9%), pneumonia (8.1%) and asthma (8.1%). Serum IgE were measured in 11 of 62 cases, ranging from 43.3 to 591 IU/ml, severed as a helpful marker. Therefore, we suggested a thorough analysis of allergen exposure, clinical history and autopsy findings is required for the diagnosis of anaphylactic death currently.
Anaphylaxis: A 2023 practice parameter update
2024, Annals of Allergy, Asthma and Immunology
This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.
Fatal and Near-Fatal Anaphylaxis: Data From the European Anaphylaxis Registry and National Health Statistics
2024, Journal of Allergy and Clinical Immunology: In Practice
Anaphylaxis is a serious systemic reaction—data on fatal and near-fatal reactions are limited.
To better understand clinical patterns and risks factors of severe anaphylaxis by a deep analysis of data from fatal and near-fatal anaphylaxis.
Data from the European Anaphylaxis Registry on fatal/near-fatal anaphylactic reactions and national data on anaphylaxis fatalities were investigated.
A total of 305 fatal/near-fatal reactions among children and adults including 35 fatalities from the European Anaphylaxis Registry were identified. The most frequent elicitors were drugs, insects, and food. Male patients (66%/60%) were more frequently affected. Male sex, higher age, concomitant mastocytosis, and cardiovascular disease were associated with a more severe outcome. With increasing reaction severity, skin symptoms were less frequently observed (45% of fatal reactions). In parallel, anaphylaxis mortality rates were studied. The data show that anaphylaxis mortality rates increased in Germany from 0.48 (2009) to 0.59 per 1,000,000 population per year (2020). This increase was apparent only in the female population. In this data set, drugs were the most frequent elicitor of anaphylaxis fatalities, and the rate for this increased over time.
We identified not only elicitors but also individual factors to be associated with an increased risk of fatal anaphylaxis. Such patients should be recognized and managed with great caution. The increase in drug-induced fatalities points to the need for a better allergological care of patients suffering from drug hypersensitivity.
Drug Allergy in Women
2023, Journal of Allergy and Clinical Immunology: In Practice
Across all settings, women self-report more drug allergies than do men. Although there is epidemiologic evidence of increased drug allergy labeling in postpubertal females, the evidence base for female sex as a risk factor for true immune-mediated drug hypersensitivity reactions (DHRs), particularly in fatal drug-induced anaphylaxis, is low. A focus on the known immunologic mechanisms described in immediate and delayed DHR, layered on known hormonal and genetic sex differences that drive other immune-mediated diseases, could be the key to understanding biological sex variations in DHR. Particular conditions that highlight the impact of drug allergy in women include (1) pregnancy, in which a drug allergy label is associated with increased maternal and fetal complications; (2) multiple drug intolerance syndrome, associated with anxiety and depression; and (3) female-predominant autoimmune medical conditions in the context of mislabeling of the drug allergy or increased underlying risk. In this review, we describe the importance of drug allergy in the female population, mainly focusing on the epidemiology and risk, the mechanisms, and the associated conditions and psychosocial factors. By performing a detailed analysis of the current literature, we provide focused conclusions and identify existing knowledge gaps that should be prioritized for future research.
Managing anaphylaxis: Epinephrine, antihistamines, and corticosteroids: More than 10 years of Cross-Canada Anaphylaxis REgistry data
2023, Annals of Allergy, Asthma and Immunology
Epinephrine is the first-line treatment for anaphylaxis but is often replaced with antihistamines or corticosteroids. Delayed epinephrine administration is a risk factor for fatal anaphylaxis. Convincing data on the role of antihistamines and corticosteroids in anaphylaxis management are sparse.
To establish the impact of prehospital treatment with epinephrine, antihistamines, and/or corticosteroids on anaphylaxis management.
Patients presenting with anaphylaxis were recruited prospectively and retrospectively in 10 Canadian and 1 Israeli emergency departments (EDs) between April 2011 and August 2022, as part of the Cross-Canada Anaphylaxis REgistry. Data on anaphylaxis cases were collected using a standardized form.
Primary outcomes were uncontrolled reactions (>2 doses of epinephrine in ED), no prehospital epinephrine use, use of intravenous fluids in ED, and hospital admission. Multivariate regression was used to identify factors associated with primary outcomes.
Among 5364 reactions recorded, median age was 8.8 years (IQR, 3.78-16.9); 54.9% of the patients were males, and 52.5% had a known food allergy. In the prehospital setting, 37.9% received epinephrine; 44.3% received antihistamines, and 3.15% received corticosteroids. Uncontrolled reactions happened in 250 reactions.
Patients treated with prehospital epinephrine were less likely to have uncontrolled reactions (adjusted odds ratio [aOR], 0.955 [95% CI, 0.943-0.967]), receive intravenous fluids in ED (aOR, 0.976 [95% CI, 0.959-0.992]), and to be admitted after the reaction (aOR, 0.964 [95% CI, 0.949-0.980]). Patients treated with prehospital antihistamines were less likely to have uncontrolled reactions (aOR, 0.978 [95% CI, 0.967-0.989]) and to be admitted after the reaction (aOR, 0.963 [95% CI, 0.949-0.977]). Patients who received prehospital corticosteroids were more likely to require intravenous fluids in ED (aOR, 1.059 [95% CI, 1.013-1.107]) and be admitted (aOR, 1.232 [95% CI, 1.181-1.286]).
Our findings in this predominantly pediatric population support the early use of epinephrine and suggest a beneficial effect of antihistamines. Corticosteroid use in anaphylaxis should be revisited.
Ethical Implications of Continuing Oral Immunotherapy After the Development of Eosinophilic Esophagitis
2023, Journal of Allergy and Clinical Immunology: In Practice
Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease requiring maintenance therapy. Traditionally, EoE has been a contraindication to oral immunotherapy (OIT) and a rationale for discontinuing treatment because OIT may induce EoE. Most, but not all patients with OIT-induced EoE experience symptom resolution and histologic remission after discontinuing OIT. Recent studies report OIT continuation even after EoE onset, despite the previously accepted standard of care. This creates clinical as well as ethical challenges for allergists treating these patients. Considering the published literature on EoE and OIT and the primary medical ethics principles of beneficence, nonmaleficence, autonomy, and justice, we discuss the ethical implications of pursuing desensitization despite the potential complications associated with EoE. When ethical principles are in opposition, shared decision-making should be employed to determine whether OIT should be continued after an EoE diagnosis. This article highlights the ethical dilemmas allergists face when determining whether patients with a diagnosis of EoE should continue OIT.

View all citing articles on Scopus

: Supported by Endo Pharmaceuticals Inc (Malvern, Pa). L.B. receives his salary from the National Institutes of Health (RO1 AI1057438 and UO1 AI100799).

: Disclosure of potential conflict of interest: L. Ma is employed by Endo Pharmaceuticals and receives stock as part of his compensation. T. M. Danoff was employed by Endo Pharmaceuticals at the time of this work and received stock as part of his compensation. L. Borish has consultant arrangements with Endo Pharmaceuticals.

View full text

Food, drug, insect sting allergy, and anaphylaxisCase fatality and population mortality associated with anaphylaxis in the United States

Background

Objective

Methods

Results

Conclusion

Section snippets

Data sources

Anaphylaxis-related hospitalizations and inpatient deaths (NIS)

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

Ann Allergy Asthma Immunol

Ann Emerg Med

Anaphylaxis: past, present and future

Allergy

Anaphylaxis

Allergy Asthma Clin Immunol

Anaphylaxis: mechanisms and management

Clin Exp Allergy

Epidemiology of anaphylaxis in the United States

Curr Allergy Asthma Rep

Epidemiology of life-threatening and lethal anaphylaxis: a review

Allergy

Anaphylaxis in children: a 5-year experience

Pediatrics

A population-based epidemiologic analysis of deaths from anaphylaxis in Florida

Allergy

Hospitalizations for anaphylaxis in Florida: epidemiologic analysis of a population-based dataset

Int Arch Allergy Immunol

Anaphylaxis in the United States: an investigation into its epidemiology

Arch Intern Med

Perspectives on anaphylaxis epidemiology in the United States with new data and analyses

Curr Allergy Asthma Rep

Food, drug, insect sting allergy, and anaphylaxis
Case fatality and population mortality associated with anaphylaxis in the United States