Food Allergy and Anaphylaxis Guidelines Draft March 2013 - EAACI

89 Pages·2013·1.26 MB·English

1 EAACI Food Allergy and Anaphylaxis Guidelines
2 Diagnosis and management of food allergy
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4 Short Title: Guidelines on food allergy
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6 Key Words: Food allergy, anaphylaxis, oral food challenge, guidelines, evidence
7 based medicine, management, oral immunotherapy,
8 Word Count: 5, 923
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10 Abbreviations:
11 APT Atopy patch test
12 BAT Basophil activation test
13 CRD Component-resolved diagnosis
14 DBPCFC Double-blind, placebo-controlled food challenge
15 EAACI European Academy of Allergy and Clinical Immunology
16 EoE Eosinophilic esophagitis
17 FA Food Allergy
18 FPIES Food protein-induced enterocolitis syndrome
19 GRADE Grading of Recommendations Assessment, Development and Evaluation
20 GERD Gastro-Esophageal Reflux Disease
21 HPF High power field
22 IgE Immunoglobulin E
23 IgG4 Immunoglobulin G4
24 LPT Lipid Transfer Proteins
25 LR Likelihood Ratio
26 NIAID National Institute of Allergy and Infectious Diseases
27 NPV Negative Predictive Value
28 NSAID Non Steroidal Anti-Inflammatory Drugs
29 OFC Oral food challenge
30 PPV Positive Predictive Value
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31 PN Peanut
32 RCT Randomised controlled trials
33 SLIT Sublingual Immunotherapy
34 SPT Skin prick test
35 sIgE Specific IgE
36 US United States
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38 ABSTRACT
39 Food allergy can result in appreciable morbidity, impact negatively on quality of life
40 and prove costly in terms of medical care. These Guidelines have been prepared by
41 the European Academy of Allergy and Clinical Immunology’s (EAACI) Guidelines for
42 Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on
43 adverse reaction to foods and three recent systematic reviews on the epidemiology,
44 diagnosis and management of food allergy. These guidelines aim to provide
45 evidence-based recommendations for the diagnosis and management of food
46 allergy. While the primary audience is allergists, these guidelines are also likely to be
47 relevant to all other healthcare professionals who need to be aware that exposure to
48 foods may trigger allergic reactions, general physicians and relevant pediatric and
49 adult specialists need, in addition, a detailed understanding of the manifestations of
50 food allergy, the role of diagnostic tests and the effective management of people with
51 food allergy. All healthcare professionals need appropriate training. Therefore, the
52 target audience is health care professionals (e.g. medical doctors, nurses,
53 pharmacists and paramedics) who are involved in the diagnosis and management of
54 food allergy, taking care of these patients in emergency departments, hospital and
55 primary care. The acute management of non-life threatening reactions is covered in
56 these guidelines, but for guidance on the emergency management of anaphylaxis,
57 readers are referred to the related EAACI Anaphylaxis Guidelines chapter.
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60 Introduction
61 Food allergy has been defined as the sub-group of adverse reactions in which
62 “immunologic mechanisms have been demonstrated” (1, 2); this term therefore
63 encompasses both immunoglobulin-E (IgE)-mediated and non-IgE-mediated food
64 allergy. Food allergy can result in considerable morbidity and in some instances
65 results in life-threatening anaphylaxis. These guidelines aim to provide evidence-
66 based recommendations for the diagnosis and management of patients with
67 suspected or confirmed food allergy of any age. Development of the guidelines has
68 been based on three systematic reviews of the epidemiology, diagnosis and
69 management of food allergy (Appendices I, II, III) with weaker forms of evidence
70 being used where there were insufficient data from more robust studies or where
71 high level evidence is practically or ethically unobtainable. These guidelines builds on
72 the previous EAACI position paper on adverse reaction to foods (3) and is
73 complementary to the other current food allergy guidelines (4), including the United
74 States (US) National Institute of Allergy and Infectious Diseases (NIAID) guidelines
75 (5). Distinctive features include a European focus and the placing of particular
76 emphasis on the practical issues associated with diagnosis and long-term
77 management of food allergy.
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79 Box 1: Key Terms
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Allergen Any substance stimulating the production of
immunoglobulin IgE or a cellular immune response,
usually proteins.
Atopic eczema/ dermatitis Chronic inflammatory skin disease characterized
by typical age related lesions with pruritus and
personal or family history of atopic disease.
Co-factors Patient related external circumstances that are
associated with more severe allergic reactions that
may also lower the threshold of reactions. They are
known also as augmentation factors.
Eosinophilic A chronic, immune/antigen-mediated disease
eosinophilicgastroenteropathies involving several tracts of the gut characterized
and esophagitis histologically by eosinophil-predominant
inflammation. Eosinophilic esophagitis is
characterized clinically by symptoms related to
esophageal dysfunction and histologically by
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eosinophilic infiltration (≥15 eosinophils per high
power field (hpf)).
Food allergy An adverse reaction to food triggered by an
immunological mechanism, involving specific IgE

(IgE mediated) or cell–mediated mechanisms (non
IgE mediated) or both IgE and cell mediated

mechanisms (mixed IgE and non IgE mediated).
Also known as food hypersensitivity.
Food desensitization A short-term tolerance that might return to initial
levels of reaction after withdrawal of the treatment.

Oral tolerance A state of local and systemic immune
unresponsiveness induced by oral administration of
innocuous antigens/ allergens
Oligo-allergenic Diet An empirical elimination diet with minimal content
of main food allergens for the given population.
Oral tolerance induction A state of local and systemic permanent immune
unresponsiveness induced by following oral
administration consumption of innocuous antigens
such as food proteins.
Prebiotic Non-digestable substances that provide a
beneficial physiological effect for the host by
selectively stimulating the favourable growth or
activity of a limited number of indigenous bacteria.
Probiotic Live microorganisms which, when administered in
adequate amounts, confer a health benefit on the
host
Sensitization Presence of specific IgE to an allergen.
Symbiotics A mixture of probiotics and prebiotics
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83 Methods
84 These Guidelines were produced using the Appraisal of Guidelines for Research &
85 Evaluation (AGREE II) approach (6, 7). This is a structured approach to guidelines
86 production that is designed to ensure appropriate representation of the full range of
87 stakeholders, a careful search for and critical appraisal of the relevant literature, a
88 systematic approach to the formulation and presentation of recommendations, and
89 steps to ensure that the risk of bias is minimized at each step of the process. We
90 provide below an overview of the approach used.
91 Clarifying the scope and purpose of the guidelines
92 The process began in January 2012 with a meeting to discuss the overall approach
93 to guidelines development, this included detailed discussions on the main aims of the
94 guidelines, the target conditions, agreeing the intended end-user for the
95 recommendations, agreeing the intended end-user group, and ensuring adequate
96 professional and lay representation in the guidelines development process.
97 Ensuring appropriate stakeholder involvement
98 Participants in the Food Allergy Diagnosis and Management Taskforce represented a
99 range of European countries, and disciplinary and clinical backgrounds (including
100 medical and nursing, hospital and primary care), and patient groups. The Food
101 Allergy Diagnosis and Management Taskforce continued to work together over the
102 ensuing 18 months through email discussions, teleconferences and several face-to-
103 face meetings.
104 Systematic reviews of the evidence
105 The initial full range of questions that were considered important were rationalized
106 through several rounds of iteration to agree to three key over-arching questions that
107 were then pursued through two formal systematic reviews of the evidence (8, 10)
108 (see Box 2).
109 Formulating recommendations
110 We graded the strength and consistency of key findings from these systematic
111 reviews to formulate evidence-linked recommendations for care (11) (Box 3). This
112 involved formulating clear recommendations and making clear the strength of
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113 evidence underpinning each recommendation. Experts identified the resource
114 implications of implementing the recommendations, barriers and facilitators to the
115 implementation of each recommendation, advice on approaches to implementing the
116 recommendations and suggested audit criteria that can help with assessing
117 organizational compliance with each recommendation.
118 Peer review
119 A draft of these guidelines was externally peer-reviewed by invited experts from a
120 range of organizations, countries and professional backgrounds. Additionally the draft
121 guidelines is made available on the EAACI website for a 2 week period in June 2013
122 to allow all stakeholders to comment. All feedback will be considered by the Food
123 Allergy Diagnosis and Management Taskforce and, where appropriate, final revisions
124 will be made in the light of the feedback received.
125 Identification of evidence gaps
126 The process of developing these guidelines has identified a number of evidence gaps
127 and we plan in future to formally prioritize these. We plan furthermore to draft outline
128 research briefs that funders can use to commission research on these questions.
129 Editorial independence and managing conflict of interests
130 The production of these guidelines was funded and supported by EAACI. The
131 funders did not have any influence on the guidelines production process, its contents
132 or on the decision to publish. Taskforce members’ conflicts of interest were taken into
133 account by the Taskforce chair as recommendations were formulated.
134 Updating the Guidelines
135 We plan to update these guidelines in 2017 unless there are important advances
136 before then.
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138 Box 2: Key over-arching questions addressed in the supporting systematic reviews
139 (8-10) Diagnosis and Management
 What is the epidemiology (i.e. frequency, risk factors and outcomes) of food allergy in
Europe and how do these vary by time, place and person?
 What is the diagnostic accuracy of tests aimed at supporting the clinical diagnosis of food
allergy?
 What is the effectiveness of pharmacological and non-pharmacological interventions for
the management of acute, non-life-threatening food allergic reactions?
 What is the effectiveness of pharmacological and non-pharmacological interventions for
the longer-term management of food allergy?

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Box3: Assigning levels of evidence and recommendations according to new grading
system ((BMJ, 2001,) (12, 13))
Level of evidence for establishing diagnostic test accuracy
Level I A systematic review of level II studies
Level II A study of test accuracy with: an independent, blinded comparison with a valid
reference standard, among consecutive persons with a defined clinical
presentation
Level III-1* A study of test accuracy with: an independent, blinded comparison with a valid
reference standard, among non-consecutive persons with a defined clinical
presentation
Level III-2* A comparison with reference standard that does not meet the criteria required
for level II and III-1 evidence
Level III-3* Diagnostic case-control study
Level IV Study of diagnostic yield (no reference standard)
Level V Case reports and expert opinion that include narrative literature, reviews and
consensus statements
Level of evidence for assessing effectiveness of interventions
Level I Systematic reviews, meta-analysis, randomized control trials
Level II Two groups, non-randomized studies (e.g. cohort, case-control)
Level III One-group non-randomized (e.g. before and after, pre-test and post-test)
Level IV Descriptive studies that include analysis of outcomes (single-subject design,
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case-series)
Level V Case reports and expert opinion that include narrative literature, reviews and
consensus statements
Grades of recommendation
Grade A Consistent level I studies
Grade B Consistent level II or III studies or extrapolations from level I studies
Grade C Level IV studies or extrapolations from level II or III studies
Grade D Level V evidence or troublingly inconsistent or inconclusive studies at any level
141 *For consistency with the Anaphylaxis Guidelines chapter level III-1 – level III-3 for
142 establishing diagnostic test accuracy were summarised as level III in this document.
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144 Epidemiology
145 Reliable and up-to-date data on the epidemiology of food allergy in Europe are
146 lacking. In order to estimate the incidence and prevalence, time-trends, and potential
147 risk and prognostic factors for food allergy in Europe, we conducted a systematic
148 review of recent (i.e. 2000-2012) European studies (8). One hundred and nine
149 articles were assessed for eligibility and 75 (comprising of 56 primary studies) were
150 included in a narrative synthesis and 30 studies in a meta-analysis. Most of the
151 studies were graded as at moderate risk of bias.
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153 A summary of the key findings is presented in Table 1. This reveals that the point
154 prevalence of self-reported food allergy was approximately six times higher than the
155 point prevalence of food allergy proven by food challenges. The prevalence of food
156 allergy was generally higher in children than in adults. While the incidence of food
157 allergy appeared to be stable over time, the prevalence may be increasing, this
158 possibly being due to secondary food allergy due to cross-reactions of food allergens
159 with inhalant allergens and/or better recognition, improved diagnosis and recording.
160 There were no consistent risk or prognostic factors for the development or resolution
161 of food allergy, but sex, age, country of residence, familial atopic history, and the
162 presence of other allergic diseases may play an important role in its etiology.
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164 Few studies employed double-blind placebo-controlled food challenge (DBPCFC) in
165 a population-based sample and so further studies are required to establish the actual
166 prevalence of objectively-confirmed food allergy in the general population. Further
167 studies are also needed to investigate the long-term prognosis of food allergy.
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