Professional Documents
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POSITION PAPER
World Allergy Organization Anaphylaxis
Guidance 2020
Victoria Cardonaa*, Ignacio J. Ansoteguib, Motohiro Ebisawac, Yehia El-Gamald,
Montserrat Fernandez Rivase, Stanley Finemanf, Mario Gellerg, Alexei Gonzalez-Estradah,
Paul A. Greenbergeri, Mario Sanchez Borgesj, Gianenrico SennaK, Aziz Sheikhl,
Luciana Kase Tannom, Bernard Y. Thongn, Paul J. Turnero,1 and Margitta Wormp,1
ABSTRACT
Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions. The
occurrence of anaphylaxis has increased in recent years, and subsequently, there is a need to
continue disseminating knowledge on the diagnosis and management, so every healthcare pro-
fessional is prepared to deal with such emergencies. The rationale of this updated position
document is the need to keep guidance aligned with the current state of the art of knowledge in
anaphylaxis management. The World Allergy Organization (WAO) anaphylaxis guidelines were
published in 2011, and the current guidance adopts their major indications, incorporating some
novel changes. Intramuscular epinephrine (adrenaline) continues to be the first-line treatment for
anaphylaxis. Nevertheless, its use remains suboptimal. After an anaphylaxis occurrence, patients
should be referred to a specialist to assess the potential cause and to be educated on prevention
of recurrences and self-management. The limited availability of epinephrine auto-injectors remains
a major problem in many countries, as well as their affordability for some patients.
Keywords: Anaphylaxis, Acute systemic allergic reaction, Adrenaline, Cofactors, Epinephrine,
Guidance, Guidelines, Antihistamines, Glucocorticoids, Food allergy, Venom allergy, Drug allergy
a
Allergy Section, Department of Internal Medicine, Hospital Vall d’Hebron, http://doi.org/10.1016/j.waojou.2020.100472
and ARADyAL research network, Barcelona, Spain Received 16 August 2020; Accepted 3 September 2020
*Corresponding author. Allergy Section, Department of Internal Medicine, Online publication date 30 October 2020
Hospital Vall d’Hebron, Passeig Vall d’Hebron 119-129, 08035, Barcelona, 1939-4551/© 2020 The Author(s). Published by Elsevier Inc. on behalf of
Spain. E-mail: vcardona@vhebron.net World Allergy Organization. This is an open access article under the CC BY-
1
These authors contributed equally to the work. NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Full list of author information is available at the end of the article
2 Cardona et al. World Allergy Organization Journal (2020) 13:100472
http://doi.org/10.1016/j.waojou.2020.100472
Southern European Allergy Societies The current update was developed based on
the previous guidelines,1 based on the best
Spanish Society of Allergology and Clinical
evidence available, such as that from systematic
Immunology
reviews performed to inform other guidelines,2 in
Taiwan Academy of Pediatric Allergy Asthma the absence of randomized controlled trials3 with
Immunology which to answer most clinical questions relevant
to anaphylaxis. A first draft of the Guidance was
Allergy, Asthma and Immunology Society of
compiled, and further discussed and refined
Thailand
through electronic correspondence and face-to-
Turkish National Society of Allergy and Clinical face meetings. The updated draft was circulated
Immunology to the WAO Board of Directors for review and
comment. The Guidance was circulated to the
Uruguayan Society of Allergology
WAO member societies for review, comments, and
voting. Comments from responding organizations
INTRODUCTION were evaluated and incorporated appropriately.
Anaphylaxis is highly likely when any one of the following 2 criteria are fulfilled:
1. Acute onset of an illness (minutes to several hours) with simultaneous involvement of the skin, mucosal
tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING:
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope,
incontinence)
c. Severe gastrointestinal symptoms (eg, severe crampy abdominal pain, repetitive vomiting), especially
after exposure to non-food allergens
2. Acute onset of hypotensiona or bronchospasmb or laryngeal involvementc after exposure to a known
or highly probable allergend for that patient (minutes to several hours), even in the absence of typical
skin involvement.
Table 2. Amended criteria for the diagnosis of anaphylaxis. PEF, Peak expiratory flow; BP, blood pressure. a. Hypotension defined as a decrease in
systolic BP greater than 30% from that person's baseline, OR i. Infants and children under 10 years: systolic BP less than (70 mmHg þ [2 x age in years]) ii. Adults
and children over 10 years: systolic BP less than <90 mmHg. b. Excluding lower respiratory symptoms triggered by common inhalant allergens or food
allergens perceived to cause “inhalational” reactions in the absence of ingestion. c. Laryngeal symptoms include: stridor, vocal changes, odynophagia. d. An
allergen is a substance (usually a protein) capable of triggering an immune response that can result in an allergic reaction. Most allergens act through an IgE-
mediated pathway, but some non-allergen triggers can act independent of IgE (for example, via direct activation of mast cells). Adapted from (26)
anaphylaxis as a serious life-threatening reaction; Some reactions present initially with isolated
however, the literature indicates that fatal and respiratory or cardiovascular symptoms;17 such
near-fatal events are rare even when reactions are presentations are not uncommon in fatal
not appropriately treated.20–25 Therefore, the anaphylaxis triggered by exposure to food and
majority of anaphylaxis reactions cannot be other allergens,18,19 and are increasingly seen
described as life-threatening in themselves; with oral immunotherapy/desensitization
although given our inability to predict reaction protocols. However, while such presentations
progression,24 we emphasize that all anaphylaxis would not constitute anaphylaxis under the
reactions must be appropriately treated with current NIAID/FAAN criteria, such reactions
intramuscular adrenaline (epinephrine, must be considered as anaphylaxis and
indistinctively used in the document) to help managed accordingly.
reduce risk of death.25
Some definitions equate anaphylaxis as a sys-
In 2005, the second US National Institute of Al- temic reaction – yet it is not uncommon for
lergy and Infectious Diseases/Food Allergy and allergic reactions to involve only the skin, remote
Anaphylaxis Network (NIAID/FAAN) symposium to the site of allergen exposure: this is clearly a
proposed clinical criteria for diagnosing anaphy- systemic manifestation, but should not be clas-
laxis,13 which were subsequently adopted by sified as anaphylaxis in the absence of poten-
WAO.1 These criteria are not a definition, but tially life-threatening compromise affecting the
rather an aid to diagnosis. At the time, it was respiratory and/or cardiovascular systems.27
acknowledged that the criteria were designed to Some triggers of anaphylaxis cause rapidly pro-
correctly identify at least 95% of episodes of gressing symptoms, but are of delayed onset
anaphylaxis (ie, with a sensitivity of >95%); after allergen exposure eg, galactose-alpha-1,3-
however, the authors identified the “need to galactose (alpha-gal allergy).28
establish their utility and determine whether
there is need for further refinement in The lack of definition of “persistent” when
prospective multicenter clinical surveys”.13 The applied to gastrointestinal symptoms in the
WAO Anaphylaxis Committee recently current NIAID/FAAN framework is ambiguous.
considered a number of issues regarding these There has long been regional differences of
criteria:26 opinion with respect to the inclusion of
6 Cardona et al. World Allergy Organization Journal (2020) 13:100472
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criteria, as shown in Table 2. The aim is to simplify Importantly, these criteria do not preclude the
the existing criteria, by combining the first 2 treatment of early, but potentially evolving sys-
NIAID/FAAN criteria and modifying the third temic reactions in the context of allergen immu-
(Fig. 1) notherapy (particularly via the sub-cutaneous
route) as anaphylaxis
1. Typical skin symptoms AND significant symp-
toms from at least 1 other organ system; OR Differential diagnosis of anaphylaxis includes
2. Exposure to a known or probable allergen for acute asthma, localized angioedema, syncope,
that patient, with respiratory and/or cardiovascular and anxiety/panic attacks, among others (see
compromise. Table 3)
Pathogenesis of anaphylaxis
Given the uncertainty over the definition of
“persistent” gastrointestinal symptoms discussed Despite expressing common clinical features,
above, this wording has been modified to “severe the underlying mechanisms of anaphylaxis may
gastrointestinal symptoms (severe crampy vary.32 Nevertheless, some of the activated
abdominal pain, repetitive vomiting), especially pathways may be common to different types of
after exposure to non-food allergens”. This ac- anaphylaxis reactions or be present
knowledges that gastrointestinal symptoms, simultaneously (Fig. 2).
particularly after exposure to non-food allergens,
IgE-mediated anaphylaxis is considered the
are indicative of anaphylaxis, without requiring
classic and most frequent mechanism. In this type,
such symptoms to become persistent in order to
anaphylaxis is triggered by the interaction of an
be treated appropriately. The choice of “severe”
allergen (usually a protein) interacting with the
rather than “persistent” is also consistent with the
allergen-specific IgE/high-affinity receptor (FcεRI)
grading system for allergic reactions used within
complex expressed on effector cells, predomi-
the US-based Consortium of Food Allergy
nantly mast cells and basophils.33 This initiates
Research (CoFAR).31 These symptoms should
intracellular signaling resulting in the release of
appear more or less simultaneously
preformed and de novo synthesis of mediators.34
The second criterion reflects the reality that the Non–IgE-mediated anaphylaxis may be immu-
occurrence of objective respiratory signs in isola- nologic or non-immunologic. The most relevant
tion following exposure to a known allergen is non-IgE-mediated immunologic mechanisms may
indicative of anaphylaxis involve the activation of pathways such as the
10 Cardona et al. World Allergy Organization Journal (2020) 13:100472
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Endogenous Exogenous
sex, age medication
cardiovascular disease physical activity
mastocytosis psychological burden
atopic disease certain elicitors
elevated tryptase sleep deprivation
ongoing infection
complement system (anaphylatoxins, C3a, and anaphylaxis through mechanisms which are not
C5a),35 the contact and coagulation system fully elucidated. Mast cells may be activated
activation,36–38 or immunoglobulin G (IgG)- through receptors such as Mas-related G-protein
mediated anaphylaxis.39–41 Non-immunologic coupled receptor member X2 (MRGPRX2) by
mechanisms have been described for some certain drugs such as neuromuscular blocking
drugs (opioids).42 Ethanol and physical factors, agents and fluoroquinolones.43,44
such as exercise, may be involved in triggering
Anaphylaxis is classified as idiopathic when no
trigger can be identified and currently represents
between 6.5 and 35.0% of cases, depending on
the studies.45 In such cases, mast cell disorders
should be ruled out. Excluding urticaria
pigmentosa does not exclude mastocytosis,
neither does a normal baseline tryptase.
Detecting KIT mutation in peripheral blood or in
bone marrow may be necessary.46,47 Also, the
role of allergens previously unrecognized (such
as alpha-Gal)48 or less straightforward to identify
(omega-5-gliadin, oleosins)49 has to be
considered.
The outcome and severity of an anaphylaxis re- affecting several organ systems more or less
action does not only depend on the elicitor itself simultaneously, should prompt immediate man-
and its dose, but also the presence of cofactors, agement. Anaphylaxis is a medical emergency that
which can impact the onset and severity of a given requires rapid identification and treatment. In pa-
reaction. Such cofactors include a variety of tients with a history of prior anaphylaxis,1,2 acute
endogenous and exogenous circumstances management consists of two steps:
(Fig. 3).25,75,76
1. Self-management by the patient using an
Importantly, mast cell disorders should also be emergency protocol, in which it is important to
ruled out even when a trigger is found, especially emphasize the key role of intramuscular
in the case of anaphylaxis after hymenoptera epinephrine (adrenaline)
stings.77
2. Additional interventions given by healthcare
Endogenous circumstances include underlying professionals once medical help has arrived,
systemic mastocytosis, unstable bronchial asthma, which must include further epinephrine (adren-
or the hormonal status of a given individual (eg, aline) if symptoms of anaphylaxis are ongoing
pre-menstrual).24,78 Exogenous factors, which
may increase the risk of an anaphylaxis reaction,
include physical exercise, infections, psycho-
logical burden, sleep deprivation, alcohol intake,
and medications.75,79–81 Among concomitant
medication, beta-blockers and angiotensin con-
verting enzyme (ACE) inhibitors have recently been
identified to influence the outcome of a severe
allergic reaction, although their effect is not fully
established.82,83 The role of cofactors is elicitor
and age-dependent and their relative relevance
varies (Table 5).79 However, in a given patient these
factors should always be considered in the history
and if possible eliminated to reduce the risk for a
severe reaction in the future.
Identification of trigger(s)
- Detailed history taking
- Confirmatory in vivo and in vitro tests
- Consultation with an allergist-immunologist or specialized health care professional
Written action plan; have patient or care-giver “teach back” when to administer epinephrine
(adrenaline) and emergency medications
Availability of epinephrine (eg, as an auto-injector) for prompt administration as early as possible
(ideally at discharge after anaphylaxis reaction)
Management of risk factors for fatality: eg, poorly controlled asthma and cardiovascular diseases, risk
taking behavior, nihilism over dangers of anaphylaxis
Recommendation to always carry a mobile-phone, especially in cases such as of exercise-induced
anaphylaxis
Prevention of recurrence
- Avoidance and/or allergen immunotherapy and/or desensitization
- Medical identification alert: eg, bracelet or wallet card
- Register in electronic or paper medical record the suspected trigger(s)
- Anaphylaxis education and training
- Public health measures eg, improved food labelling
Follow up/reassess for veracity of original cause of anaphylaxis
Table 8. Key considerations for the longer-term management of anaphylaxis
Therefore, when a patient has anaphylaxis it is route, where potentially fatal arrhythmias can
important to follow the steps outlined (Fig. 4): occur as a result of bolus administration of
remove exposure to the trigger if possible (eg, epinephrine (adrenaline)87,88 For this reason, the
discontinue administration of drugs/therapeutic intravenous route is not recommended for the
agents), assess airways, breathing, circulation, initial treatment of anaphylaxis, and if used, it
mental status, and skin, and simultaneously call should be administered in monitored patients by
emergency services, injecting epinephrine personnel with experience in diluting and
(adrenaline) intramuscularly into the vastus administering the correct doses, and preferably
lateralis of the quadriceps (antero-lateral thigh), given as an intravenous infusion via an infusion
and positioning the patient according to his/her pump. A number of protocols exist for low-dose
presenting features. Most patients should be epinephrine infusions via a peripherally-sited can-
placed in a supine position during anaphylaxis nula to treat reactions refractory to intramuscular
unless there is respiratory distress in which case a epinephrine. One in particular, developed by
sitting position may optimize respiratory effort; if Brown et al,89,90 is widely used in Australia, New
pregnant, position the patient in a semi- Zealand,91 and Spain92 as part of these
recumbent position on the left side; if uncon- countries’ national anaphylaxis guidelines, and
scious, place in the recovery position.84 The has an excellent safety and efficacy profile. In
benefit of elevation of the lower extremities case of upper airway obstruction consider adding
(Trendelenburg position) is controversial.85 nebulized adrenaline.91
In patients with anaphylaxis and symptoms of Around half of biphasic reactions occur within
bronchoconstriction, inhaled short-acting beta-2 the first 6–12 h following reaction.102 Patients with
agonists can be given (eg, salbutamol/albuterol). anaphylaxis need to be observed: this is important
Note, however, that bronchodilators given by especially in severe reactions and those requiring
inhalation or nebulization are not an alternative to multiple doses of epinephrine.86
the repeated administration of intramuscular
Fig. 4 outlines the steps considered essential for
epinephrine (adrenaline) in the presence of
appropriate treatment of anaphylaxis, which is
ongoing symptoms. In case of upper airway
needed to be urgently applied in patients who
obstruction, consider nebulized epinephrine.91 At
present with this condition.84,103
frequent and regular intervals, evaluate the
patient's blood pressure, heart rate and Anaphylaxis education and management should
perfusion, and respiratory and mental status. If be personalized according to the patient's clinical
pertinent, consider invasive monitoring. history and presentation, considering their age,
concomitant diseases, concurrent medications,
Second-line medications include beta2- and triggers.78,104
adrenergic agonists, glucocorticoids, and antihis-
tamines.93 Local guidelines may indicate different For early self-management, it is important to
drugs according to availability. The use of H1- educate the patient regarding the risk of anaphy-
antihistamines has a limited role in treatment of laxis and self-treatment of any recurrence. Patients
anaphylaxis,94 but can be helpful in relieving must be prescribed one or more epinephrine
cutaneous symptoms. Second generation (adrenaline) auto-injectors (EAI),2 although we
antihistamines may overcome unwanted side recognize that auto-injectors are not available in
effects such as sedation which may be many regions (see below). It is therefore necessary
counterproductive in anaphylaxis, but first to explain to these patients why, when, and how to
generation H1-antihistamines are currently the inject EAI or alternatives (such as marketed pre-
only available for parenteral use (eg, chlorphenir- filled epinephrine syringes or vials) where EAI are
amine diphenhydramine, clemastine). Rapid intra- not available.105 In addition, it is recommended
venous administration of first-line antihistamines that they always carry a personalized written
such as chlorphenamine can also cause hypoten- anaphylaxis emergency action plan that illustrates
sion.95 Of note, antihistamines are now a third line how to recognize anaphylaxis symptoms (eg,
treatment in some guidelines,84 due to concern tingling in the extremities, sense of heat, sense of
that their administration can delay more urgent dizziness/fainting, swollen lips-tongue-uvula,
measures such as repeated administration of shortness of breath, wheeze, stridor, collapse)
intramuscular epinephrine. and instruct them to inject epinephrine rapidly, via
the intramuscular route, in the mid-anterolateral
Glucocorticosteroids are commonly used in thigh, holding the EAI in place for about 3–10 s
anaphylaxis, with the objective of preventing pro- and then to call for medical assistance.106,107
tracted symptoms, in particular in patients with
ANAPHYLAXIS SEVERITY GRADING
asthmatic symptoms, and also to prevent biphasic
reactions (eg, intravenous hydrocortisone, or It can be difficult to grade the severity of
methylprednisolone). However, there is increasing anaphylaxis reactions. There is no overall
evidence that glucocorticosteroids may be of no consensus on which is the most appropriate sys-
benefit in the acute management of anaphylaxis, tem among the several that have been published;
and may even be harmful; their routine use is this is partly due to some being designed to grade
becoming controversial.86,96–100 reactions due to a specific trigger eg, anesthetic or
venom-related anaphylaxis may rate vomiting as a
Parenteral administration of glucagon may be more concerning symptom, in contrast to those
used in patients with anaphylaxis with no optimal used for food-related anaphylaxis. Further differ-
response to epinephrine (adrenaline), in particular, ences can be found according to the systems
in patients taking beta-blockers, despite very involved or the intensity of symptoms. A recent
limited evidence.11,101 article has compared the performance of 23
Volume 13, No. 10, October 2020 17
different systems, highlighting the differences by lack of availability and affordability of EAI or
among these (although their validation is still consultation with allergy/immunology
lacking).109 One of these, is the modification of the specialists.119
WAO grading system originally designed to
classify systemic reactions due to allergen Implementing guideline recommendations in
immunotherapy, but which has been adapted for routine clinical practice is challenging.120 The
use with systemic reactions of any cause WAO Guidelines for the Assessment and
(Table 7).110 In this classification, only some Management of Anaphylaxis in health care and
grade 3 or grades 4–5 would be consistent with community settings is a widely disseminated and
the definition of anaphylaxis, while grades 1–2 used resource (Fig. 5). They include information
constitute non-anaphylaxis. Some additional about prevention of recurrences, a global
symptoms, such as drooling or neurological agenda for anaphylaxis research, and detailed
symptoms, may be applicable in the pediatric colored illustrations linked to key concepts within
setting.111 The potential for the severity of the text.1 The recommendations in the original
reactions to change must be recognized. WAO 2011 Anaphylaxis Guidelines remain
clinically relevant and have been updated in
2012, 2013, and 201593,103,121 and were
DIAGNOSTIC TESTS IN ACUTE strengthened by the International Consensus
ANAPHYLAXIS (ICON) on Anaphylaxis in 2014.119
During acute anaphylaxis, serum tryptase levels Key considerations in the longer-term manage-
are increased from 15 min to 3 h or even longer, ment of anaphylaxis are presented in Table 8. At
after the onset; levels peak between 1 and 2 h after the time of discharge from a health care setting,
the onset with 36–40% remaining <11.4 mg/L.113 patients, at risk of another episode of
Commercial assays measure mature b-tryptase anaphylaxis, should be prescribed and taught
released upon mast cell activation and a- and b- about self-administration of epinephrine (adrena-
protryptase which is secreted constitutively (this line), and have a written personalized anaphylaxis
reflects mast cell burden rather than anaphylaxis). emergency action plan and medical identification
Although elevated levels support a diagnosis of method.2 One of the major concerns is the
anaphylaxis, normal levels do not exclude underuse of epinephrine self-infectors by patients
anaphylaxis having occurred (eg, children with who experience anaphylaxis recurrences, despite
food induced anaphylaxis).114 It is recommended having the medication.122
to evaluate baseline serum tryptase at least 24 h
after resolution of anaphylaxis symptoms, even Where EAIs are not available or affordable,
when tryptase concentration during episode physicians may recommend alternative formula-
remains within normal range. In 2010 a tions, such as a prefilled epinephrine syringe (or if
consensus equation (peak MCT should be > 1.2x this is not available, 1-mL syringe/needle and
baseline tryptase þ 2 ng/L) was proposed to epinephrine ampoule with adequate training and
diagnose acute mast cell activation.115 written instructions for drawing up the correct
Nevertheless, the consensus equation and the dose).1,105 It remains a concern that while most
other methods of comparing baseline and peak guidelines recommend a 500 mg (0.5 mg) dose
serum tryptase are unable to detect all in older children and adults >50 kg (2,86),
anaphylactic reactions.116 500 mg EAI devices are, in general, not available
in most countries. Ultrasound studies (but not
LONG-TERM MANAGEMENT OF clinical trials) suggest that the needles in 300 mg
(0.3 mg) EAI may be too short to deliver an
ANAPHYLAXIS
intramuscular dose in many patients weighing
Tailored individual anaphylaxis management more than 30 kg, while conversely, there is a risk
plans should be a part of the longer-term care of of intraosseous injection when using “junior” EAI
patients who have experienced anaphylaxis, even in young children weighing less than 15 kg.123 A
once.118 Where resources are limited, post- newly available 0.1 mg EAI has a lower dose and
discharge management is severely compromised shorter needle which may be better suited to
18 Cardona et al. World Allergy Organization Journal (2020) 13:100472
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children weighing 7.5–15 kg.124 An EAI exists that specifically assessing some prevention
provides audio and visual cues for patients.125 strategies.86
Rapidly disintegrating epinephrine (adrenaline)
sublingual tablets (RDSTs) are in development as
an alternative to injection, but are yet to be GLOBAL AVAILABILITY OF EPINEPHRINE
approved for use.126 (ADRENALINE) AUTOINJECTORS (EAI)
Guidelines recommend that patients with Epinephrine (adrenaline) is recommended as an
anaphylaxis be referred to an allergy/immunology essential medication for the treatment of anaphy-
specialist for confirmation of the suspected trigger, laxis by the World Health Organization (WHO).131
advice on prevention and, where indicated, Despite its pivotal role, the auto-injectable form is
consideration for allergen immunotherapy (eg, in- not readily available in the majority of countries.132
sect venom). Idiopathic anaphylaxis is a consider- It is limited to only 32% of all 195-world countries,
ation if a carefully-performed history, examination mostly high-income countries.133
for lesions of cutaneous mastocytosis (urticaria
pigmentosa), skin tests, and measurement of In some countries in which EAIs are not available
allergen-specific IgE levels have not revealed the through official distribution networks, they are
trigger.127 An elevated baseline tryptase available through distribution by special license
concentration may uncover systemic mastocytosis arrangements, through distribution on a “named-
in some instances, but mast cell disease may be patient” basis, or through the so-called “suitcase
present even when these levels are not trade”.133 This latter, unofficial source is unreliable
elevated.103,128 and undesirable.133 Some patients and families
can afford to order EAIs online or travel to
Vigilant avoidance prevents anaphylaxis recur-
purchase them while others cannot.134,135 EAI
rence from culprit allergens. However, it can be
costs have increased over time, which creates
frustrating and associated with impaired quality of
obvious problems for patients and families,
life, including bullying of food-allergic children,
particularly those on low incomes.136 This is a
fear of anaphylaxis during airline travel, and anxi-
major problem, and WAO strongly advocates for
ety over restrictions on exercise.129,130 In
reasonable availability.
medication-triggered anaphylaxis, avoidance of
relevant medications, and use of safe substitutes
are mandatory. If indicated, skin testing for peni- Five regional and international allergy acade-
cillin allergy, or other drugs, and graded challenge mies: AAAAI, EAACI, WAO, Asia Pacific Associa-
to rule out immediate hypersensitivity or desensi- tion of Allergy, Asthma and Clinical Immunology
tization in the absence of alternative therapies, can (APAAACI), and the Latin American Society of Al-
be attempted.1,103,121 lergy, Asthma, and Immunology (SLAAI) support
initiatives to narrow these gaps.133 A five-step ac-
Guidelines from WAO, the American Academy tion plan of advocacy was proposed:
of Allergy Asthma and Immunology (AAAAI)/
American College of Asthma Allergy and Immu- (I) To gather accurate morbidity and mortality
nology (ACAAI), and European Academy of Al- statistics on anaphylaxis.
lergy and Clinical Immunology (EAACI) all address (II) To confirm partnership: collaboration with
the recommendation of follow-up with a physician national bodies and stakeholders in order to
and if possible with an allergy/immunology reach health and/or social security
specialist.1,11,84 The WAO Guideline recommends administrations.
annual follow-up for review of prevention of
recurrence, EAI use, and optimizing control of (III) To strengthen awareness of anaphylaxis.
relevant comorbidities such as asthma.1,11,84 The (IV) To include EAI into the WHO Model List of
WAO and EAACI Guidelines note the importance Essential Medicines137
of follow-up with a dietician and a psychologist, if
relevant.84 Recently, the AAAAI/ACAAI have (V) To provide worldwide data regarding the use
published an update of their Practice Parameter, of EAIs.
Volume 13, No. 10, October 2020 19
EAI are only available by importation and with epinephrine auto-injectors; IgE: immunoglobulin E; IgG:
high costs. immunoglobulin G; FcεRI: IgE high-affinity receptor;
MRGPRX2: Mas-related G-protein coupled receptor mem-
Though there is no absolute contraindication to ber X2; NSAIDs: nonsteroidal anti-inflammatory drugs
intramuscular epinephrine for the treatment of
anaphylaxis, antihistamines and corticosteroids
Financial support
remain the most frequently drugs used to treat Not applicable.
anaphylaxis.
There is still a lack of consensus regarding how Consent for publication
long a patient with anaphylaxis should be All authors approved and agreed to publish the
observed in a healthcare setting. manuscript.
personal fees and non-financial support from Aimmune School of Medicine, University of Sydney, Sydney, Australia.
p
Therapeutics, DBV Technologies and Allergenis, personal Department of Dermatology and Allergology, Charite-
fees and other from ILSI Europe and UK Food Standards Universitätsmedizin, Berlin, Germany.
Agency, outside the submitted work; current Chairperson
of the WAO Anaphylaxis Committee, and joint-chair of the
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