Clinic Rev Allerg Immunol (2018) 54:366–374
DOI 10.1007/s12016-015-8503-x
The Epidemiology of Anaphylaxis
Joyce E. Yu 1 & Robert Y. Lin 2
Published online: 10 September 2015
# Springer Science+Business Media New York 2015
Abstract Anaphylaxis is a dramatic expression of systemic
allergy. The lifetime prevalence of anaphylaxis is currently
estimated at 0.05–2 % in the USA and ~3 % in Europe.
Several population-specific studies have noted a rise in the
incidence, particularly in the hospitalizations and ER visits
due to anaphylaxis. The variable signs and symptoms that
constitute the diagnostic criteria for anaphylaxis, the dif-
ferences in diagnostic algorithms, and the limitations in
the current coding systems have made summarizing epide-
miologic data and comparing study results challenging.
Nevertheless, across all studies, the most common triggers
continue to be medications, food, and venom. Various risk
factors for more severe reactions generally include older
age, history of asthma, and having more comorbid diseases.
Interesting seasonal, geographic, and latitude differences have
been observed in anaphylaxis prevalence and incidence rates,
suggesting a possible role of vitamin D and sun exposure in
modifying anaphylaxis risk. While the incidence and preva-
lence of anaphylaxis appear to be increasing in certain popu-
lations, the overall fatality rate remains relatively low.
Keywords Anaphylaxis . Epidemiology . Prevalence .
Incidence . Risk factor . Triggers . Biphasic . Fatality
* Joyce E. Yu
jeyu74@gmail.com
1
Division of Allergy, Immunology, and Rheumatology, Department of
Pediatrics, Morgan Stanley Children’s Hospital of New
York-Presbyterian, Columbia University Medical Center, New
York, NY, USA
2
Department of Medicine, Weill Cornell Medical Center,
New York, NY, USA
Introduction
Anaphylaxis is a clinical diagnosis which the National Insti-
tute of Allergy and Infectious Diseases (NIAID) currently
defines as an acute, potentially life-threatening systemic aller-
gic reaction [1] which can be caused by numerous triggers.
Anaphylaxis occurs when the exposure to a suspected or
known trigger causes systemic release of histamine and other
mediators of allergic inflammation that lead to a varying
constellation of potentially life-threatening allergic symp-
toms including, but not limited to, respiratory compromise,
hypotension, severe urticaria, and angioedema.
In this review, the NCBI PubMed database was queried
for publications relevant to different epidemiologic aspects
of anaphylaxis including triggers, risk factors, trends, and
clinical features, as well as practice statement and guide-
lines. A literature review of the retrieved results was then
performed to summarize the current knowledge of anaphy-
laxis epidemiology.
General Considerations
To date, several types of analyses have been performed to
determine the incidence and prevalence of anaphylaxis in-
cluding database mining, population-based questionnaires,
chart reviews and systemic reviews, and meta-analyses
(Table 1). Observational studies, such as retrospective chart
reviews and database analyses, have been the more frequently
employed methods to assess the epidemiology of anaphylaxis.
In contrast, few studies in systematic reviews have been
included in meta-analyses because wide variations in data
collection, study design, and data analysis have limited the
ability to compare studies [2, 3]. The multiple diagnostic
criteria for anaphylaxis have presented challenges in describing
Clinic Rev Allerg Immunol (2018) 54:366–374 367

Table 1 Types of epidemiologic studies on anaphylaxis

Study type Selected studies Source(s) Location(s) Population Time period

Cross-sectional database Jerschow et al. [10] Multiple Cause of Death USA Adults 1999–2010
analysis (public health Database
records, disease registry,
research, commercial
insurance)
Lin et al. [17] New York Statewide Planning NY Pediatric 1990–2006
and Research Cooperative Adults
System (SPARCS)
Poulos et al. [19] National Mortality Database Australia Pediatric 1993–1994,
Adults 2004–2005
Worm et al. [29] Anaphylaxis registry, Berlin Germany, Austria, Pediatric 2006–2013
emergency physician Switzerland Adults
service, ADAC nationwide
air rescue service
Worm et al. [30] European Anaphylaxis Europe (Austria, Bulgaria, Pediatric 2011–2014
Registry France, Germany, Greece, Adults
Ireland, Italy, Poland,
Spain and Switzerland)
Bohlke et al. [16] Group Health Cooperative Washington, USA Pediatric 1991–1997
HMO
Bohlke et al. [62] Centers for Disease Control Seattle, WA, USA Pediatric 1991–1997
and Prevention’s Vaccine Oakland, CA, USA
Safety Datalink (VSD) Portland, OR, USA
Los Angeles, CA, USA
Simon et al. [72] Florida Department of Health, Florida, USA Pediatric 1996–2005
Office of Vital Statistics Adults
death certificates
Camargo et al. [74] NDC Health, Pharmaceutical USA Pediatric 2004
Audit Suite Adults
Simons et al. [76] University of Manitoba Health Manitoba, Canada Pediatric 1995–1999
Research Database/Drug
Programs Information Net-
work
Ma et al. [84] Nationwide Inpatient Sample USA Adults 1999–2009
(NIS; 1999–2009), the
Nationwide Emergency
Department Sample
(NEDS; 2006–2009), and
Multiple Cause of Death
Data (MCDD; 1999–2009)
Turner et al. [85] Hospital Episodes Statistics England, UK Pediatric 1992–2012
database, Patient Episode Wales, UK Adults
Database for Wales,
National Health Service
Business Services
Authority Prescription
Cost Analysis databases
Renaudin et al. [88] Allergy Vigilance Network Europe (multiple countries) Pediatric 2002–2010
Adults
Retrospective chart Dibs et al. [21] Single ED, inpatient, Philadelphia, PA, USA Pediatric 1990–1994
review (single center, operating room
multi-center)
Rudders et al. [22] Multiple ED Boston, MA, USA Adults 2001–2006
Calderon et al. [24] Single ED Puerto Rico Adults 2007–2009
Capps et al. [25] Ambulance services Manchester, UK Pediatric 2007–2008
Adults
Lauritano et al. [26] Single ED Alessandria, Italy Adults 2009-2010
Harduar-Morano et al. [67] Multiple ED Florida, USA Pediatric 2005–2006
Adults
Braganza et al. [79] Single ED Australia Pediatric 1998–2001
368 Clinic Rev Allerg Immunol (2018) 54:366–374

Table 1 (continued)

Study type Selected studies Source(s) Location(s) Population Time period

Population studies Decker et al. [15] Rochester, MN Pediatric 1990–2000

(telephone surveys, Adults
patient questionnaires)
Wood et al. [20] USA Pediatric 2011
Adults
Tejedor Alonso et al. [27] Alcorcon, Spain Pediatric 2004–2005
Adults
Review/systematic review Panesar et al. [3] Europe (multiple countries) Pediatric 2000–2012
Adults
Rubin et al. [7] Multiple Pediatric 2001–2012
Adults
Chipps et al. [82] Multiple Pediatric 2007–2012
Cohort Brown et al. [87] Hobart, Tasmania, Australia Pediatric 1990–1999
Adults
Vezir et al. [89] Ankara, Turkey Pediatric 2010–2012
Case control Gonzalez-Perez et al. [38] London, UK Pediatric 1996–2005
Adults
Meta-analysis Umasunthar et al. [2] Multiple Pediatric 1946–2012
Adults
Umasunthar et al. [57] Multiple Pediatric 1946–2012
Adults

the overall epidemiologic patterns for anaphylaxis [1, 4–7], and
the global prevalence and incidence of anaphylaxis are difficult
to estimate due to the heterogeneity of the study populations.
Furthermore, there are few published studies from resource-
limited countries on anaphylaxis epidemiology [8].
The use of diagnostic codes to include patients in retrospec-
tive chart reviews or database analyses could lead to under or
over-reporting of anaphylaxis [9]. There are currently limited
ICD9 and ICD10 codes specific to anaphylaxis, and the codes
do not cover all the possible symptoms or triggers. For exam-
ple, the ICD10 system includes a specific code for drug-
induced anaphylaxis but codes for venom- and food-
specific-induced anaphylaxis are not included [10]. Creating
ICD10 codes specific for anaphylaxis caused by each major
class of foods could impact dietary avoidance recommenda-
tions and clinical management. There may also be variability
in coding practices [11], especially because the clinical defi-
nition of anaphylaxis is complex. Adding codes that corre-
spond to the different NIAID clinical definitions of anaphy-
laxis may help to identify more cases of anaphylaxis. For
example, current ICD10 codes refer to only anaphylactic
shock due to an unknown or unspecified trigger, but it would
be important to include an ICD10 code that covers the range
of anaphylactic reactions that may be caused by an unidenti-
fied trigger. In fact, the 2014 guidelines from the EAACI
Taskforce on Anaphylaxis has identified gaps in simplifying
the diagnostic criteria and the clinical definition of anaphylax-
is for ED staff, as well as in the coding criteria for anaphylaxis
to allow accurate epidemiologic reporting [11]. In addition,
considering the variable expressions of disease, algorithmic
schemes for identifying anaphylaxis may be useful in
enhancing the sensitivity of anaphylaxis diagnoses especially
in hospitalized patients in whom the discharge diagnosis may
only rely on the signs and symptoms driving admission.
According to the International Consensus on (ICON) ana-
phylaxis collaborative report, the separate practice guidelines
put forth by the World Allergy Organization (WAO); the
American Academy of Allergy, Asthma, and Immunology
(AAAAI)/American College of Allergy, Asthma, and Immu-
nology (ACAAI); and the European Academy of Allergy and
Clinical Immunology (EAACI) currently provide limited or
no information about anaphylaxis epidemiology [8, 11–13].
As such, the report has proposed a research agenda addressing
the unmet needs for more valid and reliable data about
prevalence, incidence, and mortality rates; development
of more anaphylaxis-specific diagnostic ICD9 and ICD10
codes; and more studies to estimate prevalence in resource-
limited countries [13].
Prevalence and Incidence
According to the 2006 report by the American College of
Allergy Asthma and Immunology (ACAAI) anaphylaxis
workgroup, the lifetime prevalence of anaphylaxis in the
USA is currently estimated to be between 0.05 and 2 % [9].
The 2006 NAIAD report estimates the incidence to be around
10–20/100,000 population per year [1]. A report by Yocum
et al. found an occurrence rate of 30 per 100,000 person-years
and an average incidence rate of 21 per 100,000 person-years
Clinic Rev Allerg Immunol (2018) 54:366–374
over a 5-year period in Olmsted County, Minnesota [14].
However, a 2008 population study from Minnesota found
the modest rise in incidence from 46.9 per 100,000 to 58.9
per 100,000 person-years during a 10-year period [15]. Al-
though Bohlke et al. did not find an increase in incidence in
children under the age of 18 years [16], a review of a New
York state database reported a fourfold increase in anaphylaxis
hospitalizations in patients under 20 years [17], and a later
study out of New York state described a statistically signifi-
cant rise in anaphylaxis hospitalizations in patients under
20 years from 2.1 to 3.7 per 100,000 person-years [18]. Sim-
ilarly, Poulos et al. noted a rise in anaphylaxis hospitalizations
in Australian children aged 0–4 years from 4.1 to 19.7 per
100,000 person-years, especially a 5.5-fold increase in food-
triggered reactions [19]. Wood et al. recently reported an even
higher prevalence of anaphylaxis in a 2014 study in which
they conducted two telephone surveys of a randomized sam-
ple of the US population [20]. Of the 1000 respondents ana-
lyzed, the authors found that ~7.7 % self-reported having ex-
perienced an anaphylactic reaction with approximately 5.1 %
having likely anaphylaxis according to clinical criteria [20].
However, the authors admit that the survey lacked validation
and was subject to potential recall and recruitment bias.
The majority of studies have assessed the occurrence of
anaphylaxis in the emergency department (ED), ambulatory
care setting, and in hospitalized patients [16, 21, 22]. As men-
tioned above, the frequency of anaphylaxis especially present-
ing to the ED has risen over the past several years, with one
report citing a 58 % rise [23]. The US telephone survey by
Wood et al. found that anaphylaxis episodes occurred most
commonly at home [20], and because of the varying nature
of anaphylactic reactions, some of these patients may never
present to a physician, suggesting that the exact incidence
of anaphylaxis in the community is likely underestimated
[9, 20, 24].
Geographic Differences
Internationally, the majority of the studies hail from the USA
and Europe with some epidemiologic studies originating from
other continents, such as South America, Australia, and Asia.
As with the studies set within the USA, the European studies
also report a variable incidence and prevalence of anaphylaxis
[3]. A report from Manchester, UK, of patients presenting to
paramedics and first aides estimated 0.2 % of emergency cases
were due to anaphylaxis [25]. The experience in an Italian ED
found that 0.7 % of all visits in 1 year were diagnosed with
acute allergic reactions and 4.6 % of these patients had ana-
phylaxis, although they also note that an additional 17.7 % of
this group presented with two or more clinical symptoms [26].
A population study from Spain showed that the incidence of
anaphylaxis was 103.37 per 100,000 person-years with
369
slightly higher rates in children aged 0–4 years [27]. In the
same study, females in the 10 years and older group were more
likely to have anaphylaxis [27]. A systematic review by
Panesar et al. found a reported range of incidence from 1.5
per 100,000 to 32 per 100,000 person-years [3]. Using data
that was pooled from three selected population-based studies,
they determined that an overall estimated prevalence of ana-
phylaxis in Europe was 3 % [3].
Whereas antibiotics are the most common drug trigger in
the USA, a review of 313 patients in Portugal with a history of
drug-induced anaphylaxis revealed that the most common
trigger was NSAIDS followed by antibiotics and anesthetics,
respectively, which the authors attributed to different prescrib-
ing patterns [28]. In contrast to the US data, a report by Worm
et al. of the anaphylaxis registry in Germany, Austria, and
Switzerland found that the most common trigger was insect
venom followed by food and drugs, respectively [29, 30].
They are also noted that patients were administered epineph-
rine as infrequent as 14.5 % of the time. A study by Calderon
et al. which reviewed the charts of 135 adults presenting to the
ED reported that 4.4 % were diagnosed with anaphylaxis and
another 23 % (25 of 129) of those diagnosed with an allergic
reaction met clinical criteria for anaphylaxis [24]. In this study,
the most common triggers were food or medications.
Of the studies originating from South America, a 5-year
retrospective chart review from Caracas, Venezuela, of ambu-
latory patients found that 179 out of 2421 (7.39 %) cases had
had one or more episodes of anaphylaxis [31]. A study by
Hoyos-Bachiloglu et al. reported that the national admission
rate for anaphylaxis was 1.41 per 100,000 person-years [32].
As for recent epidemiologic studies performed in Asia, one
report from Thailand estimated a particularly high incidence
of anaphylaxis in the adults presenting to their single ED at
652 per 100,000 person-years [33], although a study by an-
other group from Thailand estimated the incidence in admitted
patients at 55.45 per 100,000 person-years [34]. A Singapore
study of 98 pediatric patients who were admitted for anaphy-
laxis from 2005 to 2009 found that food (63 %), especially
peanuts and medications (30 %), were the most common trig-
gers and that the patients experienced a 3.6 % rate of biphasic
reactions [35], which generally concur with studies from other
countries. One retrospective chart review of 108 patients who
developed anaphylaxis while hospitalized in Beijing, China,
between 1990 and 2013 found that most of the patients were
admitted after 2005 (68.5 %), most were female, and that
89.5 % of anaphylactic events were presumably triggered by
medications [36].
Risk Factors
Guidelines from the WAO have reported that infants, teen-
agers, pregnant women, and elderly are at higher risk for
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anaphylaxis due to various reasons [8]. It has been spec-
ulated that some of these populations may also be less
capable of tolerating a systemic insult. Analysis by Clark
et al. of almost 12,000 ED visits or hospitalizations from
two MarketScan Research databases showed that severe
anaphylaxis was associated with older age and more
preexisting comorbid conditions [37]. As indicated in the
ICON document, cardiovascular disease and especially
asthma are well-recognized risk factors for anaphylaxis
[13, 38]. In patients with food allergy, especially children,
asthma is known to be associated with more severe reac-
tions and an increased risk of anaphylaxis [39, 40]. Co-
factors such as exposure to cross-reactive allergens, con-
current use of other medications such as cardiac medica-
tions and NSAIDs, alcohol consumption, exercise and
stress, and menstruation have been acknowledged to exac-
erbate anaphylaxis [41]. Furthermore, as to be expected,
the presence of multiple risk factors and co-factors is more
commonly seen in adults than in children.
It has been well-reported that patients with underlying mast
cell disease may be at higher risk for anaphylaxis, particularly
in reaction to venom [42–45]. In a cohort of 379 subjects with
insect sting anaphylaxis, elevated baseline serum tryptase
levels were detected in 44 (11.6 %) subjects, of whom 31
(70.5 %) had a prior history of anaphylaxis, and 7.9 % of
the 379 patients were ultimately diagnosed with monoclonal
mast cell activation or systemic mastocytosis [43]. In another
series of 84 patients with systemic mastocytosis, 43 % had at
least one episode of anaphylaxis and 53 % had severe reac-
tions to Hymenoptera venom [46]. Currently, the joint ACAAI
and AAAAI practice parameters for stinging insect hypersen-
sitivity recommend obtaining baseline serum tryptase for a
possible mast cell activation disorder [47].
Triggers
Anaphylaxis is a clinical syndrome that can be caused by
various classes of triggers. Among several studies reviewed
herein, the triggers most frequently identified were medica-
tions, foods, and insect stings (Table 2). Often, exact triggers
are not identified if at all [48] during the acute event, leading
to often misdiagnosing or underdiagnosing anaphylaxis, and
inciting triggers may vary by setting. In a study by Jerschow
et al., outpatient fatal anaphylaxis was more associated with
food whereas drug-induced anaphylaxis was more common
with hospitalized inpatients [10].
The most common etiology for anaphylaxis in adults is
drugs. The most commonly associated medications being an-
tibiotics, NSAIDs, and immunomodulators or biological
agents [8]. Particular anesthetics, such as the neuromuscular
blocking agents [49], contrast agents and dyes [15, 28, 50, 51],
and chemotherapeutic agents [52] are also frequently cited. A
Clinic Rev Allerg Immunol (2018) 54:366–374
Table 2 Common
triggers for anaphylaxis Anaphylaxis triggers
Drugs
Antibiotics
NSAIDS
Immunomodulators
Neuromuscular agents
Contrast agents
Food
Peanut
Tree nut
Shellfish
Insect venom
Hymenoptera
Vespula
Fire ant
review by Pichichero et al. reports that the risk of anaphylaxis
to penicillin appears to range from 0.015 to 0.004 % with a
fatality rate of 0.0002 to 0.0015 % [53]. Medications were the
most commonly reported trigger overall at 56.5 % in the
population study by Wood et al. [20].
Food is often implicated in anaphylaxis, and in infants and
young children, food is the most common trigger [10, 20, 54].
Of food-triggered reactions, peanuts and tree nuts were most
frequently identified in several studies, but milk, egg, and
shellfish were also commonly documented [5, 22, 55, 56].
Several studies show that the incidence of food-induced ana-
phylaxis in children is rising [23, 55]; however, a meta-
analysis by Umasunthar et al. estimated the incidence of
food-triggered fatal anaphylactic reactions to be rare at 1.35–
2.71 per million person-years [57].
Venom has been estimated to cause between 1.5 and 34 %
of all cases of anaphylaxis [42]. The presence of concomitant
atopic disease such as allergic rhinitis, food allergy, or asthma
also increases the risk for insect sting anaphylaxis [3].
Food-dependent exercise-induced anaphylaxis (FDEIA) is
an important, albeit less prevalent, consideration in anaphy-
laxis etiologies but can be challenging to diagnose given the
varying period of time between food ingestion and exercise
that could trigger symptoms [58]. Classic triggers for FDEIA
include wheat, celery, and shellfish; however, any food can be
associated [58]. Delayed reactions to red meat triggered by
galactose-α-1,3-galactose [59], an oligosaccharide present in
red meat, and cases of underlying systemic mastocytosis are
also increasingly recognized as possible etiologies for what
may otherwise appear as idiopathic anaphylaxis [48]. Rare
anaphylactic reactions to other triggers have been reported in
the literature including but not limited to supplements [60],
honey [61], vaccines [62–64], chemicals and latex [65], and
dust mite ingestion [31].
Clinic Rev Allerg Immunol (2018) 54:366–374
Allergy immunotherapy also poses a risk for anaphylaxis;
however, there have been very few reports of fatalities asso-
ciated with anaphylaxis caused by immunotherapy [66]. A 4-
year survey of allergist/immunologists experience with sub-
cutaneous allergen immunotherapy revealed only one death
and an overall rate of systemic allergic reactions at 0.1 % [66].
Often though, the specific trigger may not be identified
when the reaction is occurring acutely especially if the reaction
is occurring for the first time, and sometimes triggers for ana-
phylaxis may only be retrospectively identified at a follow-up
evaluation. One study of ED records in Florida found that only
37 % of patients could pinpoint a specific trigger upon presen-
tation [67], and a review by Lieberman et al. reports that up to
60 % of cases referred to a specialist are considered idiopathic
and appears to be more common in adults and in women [48].
Trends in Biphasic Reactions
The prevalence of biphasic reactions is difficult to assess.
Patients may not be adequately monitored in the ED after
the initial acute reaction, and symptoms occurring later may
not be recognized as being related to the initial reaction. Pa-
tients are generally observed at least 4–6 h for the possibility
of a biphasic reaction [68, 69]. A study from Switzerland of
over 250,000 patients who presented to the ED found that
4.5 % of the patients presenting with anaphylaxis had biphasic
reactions which were not associated with any specific risk
factors [70]. Grunau et al. reviewed over 2800 adult patients
presenting to the ED and found, in contrast, that few (0.18 %)
of allergic or anaphylactic reactions were associated with a
significant biphasic reaction [71]. No deaths were reported
in either study [70, 71].
Variation by Season and Latitude
A possible variation in anaphylaxis occurrence by time of the
year has been suggested by a number of studies. Simon et al.
found that most of the life-threatening reactions occurred in
the spring and summer [72]. A study by Vassallo et al. of over
3700 patients in Boston found that, in children under 18 years
of age, food-induced anaphylaxis was more common in those
who were born in the fall (26 %) and winter (28 %) versus
spring (21 %) and summer (25 %). In the older group, they did
not see an increase in fall/winter births. However, just as vita-
min D has been associated with the rise of asthma and atopic
dermatitis, the authors propose that perhaps vitamin D status
and amount of exposure to UVB light may account of these
seasonal differences.
An US analysis of 17.3 million ED visits in different geo-
graphic locations by Rudders et al. found that the Northeast
states had a higher odds ratio than the South states for visits for
371
acute allergic reactions including anaphylaxis of 1.13 (95 %
CI, 1.01–1.27) [73]. Mulla et al. also note similar findings in
which younger New York residents were more likely than
Florida residents to be hospitalized for anaphylaxis [18].
Using epinephrine prescribing patterns as an indirect measure
of anaphylaxis incidence, Camargo et al. reported that the
highest number of epinephrine prescriptions were written in
Massachusetts (11.8 per 1000 persons) as compared to a sun-
ny state like Hawaii (2.7 per 1000 persons) [74]. The reverse is
seen in the southern hemisphere where a 2009 study out of
Australia by Mullin et al. showed that epinephrine prescrip-
tion rates and hospital admission rates were higher in the
southern regions than in the northern regions, but where there
is more sun exposure, a pattern that was also noted from a
study out of Chile [32]. All these studies appear to suggest that
the incidence of anaphylaxis may vary with latitude and fur-
ther support a possible role of sun exposure and vitamin D in
the occurrence of anaphylaxis.
Variation by Age and Sex
Anaphylaxis can occur at any age, even in infants [40, 75–77].
Data from an European anaphylaxis registry revealed that over
one quarter of cases occur under 18 years of age [30]. Food is
the most common trigger for young children, as opposed to
adults over age 30 years in whom medications become the
more prevalent trigger. Cutaneous symptoms are the most
common in children and adults; however, children more
frequently experience respiratory symptoms in contrast to
adults who are more likely to have cardiovascular symp-
toms [4, 5, 78, 79]. Whereas rates of biphasic reactions as
high as 20 % have been reported in adults [80], a pedi-
atric series by Lee et al. reports about 6 % of hospitalized
children had biphasic reactions with 3 % having signifi-
cant reactions [81]. In addition, delayed administration of
epinephrine was associated with increased biphasic reactions
[81, 82]. With regard to outcomes in pediatric patients, Rubin
et al. note that there are very limited randomized, controlled
trials assessing epinephrine treatment or treatment with corti-
costeroids and antihistamines specifically in children [7], even
though there is fairly strong evidence that timely administra-
tion of epinephrine is the recommended first-line treatment for
anaphylaxis [1].
In the pediatric population, anaphylaxis appears to occur
more commonly in boys and particularly in older children and
adolescents, possibly in part due to increased risk-taking [16,
79]. On the other hand, in the adult population, anaphylaxis is
most often diagnosed in middle-aged females [20]. In general
though, older age appears to be more associated with severe,
fatal anaphylaxis [8, 10, 83], likely due to other comorbid,
underlying medical issues and decreased ability to tolerate
the symptoms of a severe reaction [8, 83].
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Fatality and Mortality
Examination of ED discharge records and death certificates
over a 10-year period from three US databases including the
Nationwide Inpatient Sample (NIS), the Nationwide Emer-
gency Department Sample (NEDS), and Multiple Cause of
Death Data (MCDD) showed that the case fatality rate ranged
between 0.25 and 0.33 % of hospitalizations or ED presen-
tations for anaphylaxis [84]. Although the average fatality
rate remained consistent at ~0.3 % in this study, the rate of
hospitalization for anaphylaxis was noted to increase by
2.23 % annually [84]. Likewise, a recent study from the
UK found that while the incidence of anaphylaxis-related
hospitalizations was dramatically increased from 1992 to
2002, the case fatality rate remained stable [85], presum-
ably due to improved recognition. In terms of trigger-
specific reactions, Bock et al. estimated from pooled studies
that food allergy accounted for approximately 150–200
deaths annually [86].
Analysis of the US National Mortality Database over an
11-year period by Jerschow et al. showed that fatal anaphy-
laxis from all causes except venom was associated with
African-American race and older age whereas anaphylaxis
from venom was associated with white race, older age, and
male sex [10]. The highest risk of fatality from anaphylaxis
was also associated with persons 60 years and older in the UK
according to a report by Turner et al. [85].
Delayed use of intramuscular epinephrine has been associ-
ated with increased risk for fatality, and several studies reveal
a continued disparity between the diagnosis of anaphylaxis
and frequency of epinephrine treatment [8, 9, 11]. About
73 % of patients received epinephrine in a study by Brown
et al. [87] and only 57.9 % in a study by Renaudin et al. [88].
Similar rates were reported by Calderon et al. with only 63 %
of recognized and 4 % of unrecognized anaphylaxis cases
being treated with epinephrine in the ED [24]. Rates as low
as treatment of 8 % of patients have been cited, while the
majority of studies report treatment rates between 30 and
60 % [39, 89–92].
Summary and Conclusions
Anaphylaxis is a clinical diagnosis comprising of multiple
clinical features, making accurate reporting of incidence and
prevalence difficult. In general, the incidence and prevalence
appear to be higher than previously thought particularly in
certain patient groups and likely due to improved diagnosis
and increased awareness. Although overall fatality rate is
low, morbidity associated with anaphylaxis still significantly
impacts acute medical resource utilization. Clarification of
global prevalence rates and better recognition of the risks
and triggers in specific populations may help support
Clinic Rev Allerg Immunol (2018) 54:366–374
anaphylaxis education and research programs, improve the
quality of health services for anaphylaxis in the community,
and facilitate more prompt treatment of these patients.
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