1 GUIDELINES FOR THE 2 DIAGNOSIS AND 3 MANAGEMENT OF FOOD 4 ALLERGY 5 TABLE OF CONTENTS 6 Section 1 Introduction ................................................................................................... 1 7 Section 2 Definitions, Prevalence, and Epidemiology of Food Allergy ....................... 7 8 Section 3 Natural History of Food Allergy and Associated Disorders ....................... 21 9 Section 4 Diagnosis of Food Allergy .......................................................................... 38 10 Section 5 Management of non-acute allergic reactions and 11 Prevention of Food Allergy .............................................................................................. 61 12 Section 6 Diagnosis and Management of Food-Induced Anaphylaxis and 13 Other Acute allergic Reactions to Foods .......................................................................... 91 14 Appendices 15 Appendix A: Coordinating Committee Member Organizations .................................... 111 16 Appendix B: Expert Panel Members ............................................................................. 112 17 Appendix C: Sample Of An Anaphylaxis Emergency Action Plan .............................. 116 18 i 19 SECTION 1 INTRODUCTION 20 1.1 OVERVIEW 21 Food allergy is an important public health problem that affects adults and children and 22 may be increasing in prevalence. Despite the risk of severe allergic reactions and even 23 death, there is no current treatment other than allergen avoidance and treating the 24 symptoms associated with severe reactions. Moreover, the diagnosis of food allergy may 25 be problematic given that non-allergic food reactions, such as food intolerance, are 26 frequently confused with food allergies. Additional concerns relate to the differences in 27 the diagnosis and management of food allergy in different clinical practice settings. 28 Due to these concerns, the National Institute of Allergy and Infectious Diseases (NIAID), 29 part of the National Institutes of Health, working with more than 30 professional 30 organizations, Federal agencies, and patient advocacy groups, led the development of 31 “best practice” clinical guidelines for the diagnosis and management of food allergy, 32 henceforth referred to as the Guidelines. Based on a comprehensive review and objective 33 evaluation of the recent scientific and clinical literature on food allergy, the Guidelines 34 were developed by and designed for allergists and clinical researchers and practitioners in 35 the areas of pediatrics, family medicine, dermatology, gastroenterology, emergency 36 medicine, pulmonary and critical care medicine, and others. 37 The Guidelines focus on diseases that are defined as food allergy (see Section 2.1), and 38 include both immunoglobulin E (IgE)-mediated reactions to food and some non-IgE- 39 mediated reactions to food. The Guidelines do not discuss celiac disease, which is an 40 immunologic non-IgE-mediated reaction to certain foods. Although this is an important 41 immune-based disease involving food, existing clinical guidelines for celiac disease will 42 not be restated here.1, 2 43 In summary, the Guidelines 44 ● Provide concise recommendations to a wide variety of healthcare providers on 45 how to diagnose food allergy, manage ongoing food allergy, and treat acute food 46 allergy reactions. 47 ● Identify gaps in the current scientific knowledge to be addressed through future 48 research. 49 ● Identify and provide guidance on points of current controversy in patient 50 management. 51 Finally, these Guidelines do not address the management of food-allergic patients outside 52 of clinical care settings (e.g., schools and restaurants) or the related public health policy 53 issues. These issues are beyond the scope of this document. 1 54 1.2 HOW THE GUIDELINES WERE DEVELOPED 55 1.2.1 THE COORDINATING COMMITTEE 56 NIAID established a Coordinating Committee (CC), whose members are listed in 57 Appendix A, to oversee the development of the Guidelines, review the draft Guidelines, 58 and approve the final Guidelines. The CC was also responsible for the review of drafts 59 for accuracy, practicality, clarity, and broad utility of the recommendations in clinical 60 practice. The CC members were professional organizations, advocacy groups, and 61 Federal agencies, each of which appointed one or more representatives to serve on the 62 Committee. Each organization, group, or agency had a single vote on the CC. Each 63 representative was vetted for financial conflict of interest (COI) by NIAID staff. Potential 64 COIs were posted on the NIAID Web site 65 http://www3.niaid.nih.gov/topics/foodAllergy/clinical/Who/ExpertPanel/disclosure.htm. 66 1.2.2 THE EXPERT PANEL 67 The CC convened an Expert Panel (EP) in March of 2009 that was chaired by Joshua 68 Boyce, MD (Brigham and Women’s Hospital, Boston, MA). Panel members were 69 specialists from a variety of relevant clinical, scientific, and public health areas (see 70 Appendix B). Each member was vetted for financial COI by NIAID staff and approved 71 by the CC. Potential COIs were posted on the NIAID Web site provided in Section 1.2.1. 72 The charge to the EP was to use an independent, systematic literature review (see Section 73 1.2.3), in conjunction with consensus expert opinion and EP-identified supplementary 74 documents, to develop guidelines that provide a comprehensive approach for diagnosing 75 and managing food allergy based on current state-of-the-science. 76 The EP organized the Guidelines into five major topic areas: 77 1. Definitions, prevalence and epidemiology of food allergy 78 2. Natural history of food allergy and associated disorders 79 3. Diagnosis of food allergy 80 4. Management of non-acute food allergic reactions and prevention of food allergy 81 5. Diagnosis and management of food-induced anaphylaxis and other acute allergic 82 reactions to foods 83 Subtopics were developed for each of these five broad categories. 84 1.2.3 THE INDEPENDENT, SYSTEMATIC LITERATURE REVIEW AND 85 REPORT 86 RAND Corporation prepared an independent, systematic literature review and evidence 87 report on the state of science in food allergy. RAND Corporation had responded to the 88 NIAID Request For Proposal AI2008035, “Systematic Literature Review and Evidence 89 Based Report on Food Allergy,” and was subsequently awarded the contract in 90 September, 2008. The contract’s Principal Investigator was Paul G. Shekelle, MD, PhD, 91 an internationally recognized expert in the fields of practice guidelines and meta-analysis. 2 92 NIAID and the EP developed an extensive set of key questions, which were further 93 refined in discussions with the RAND Corporation. Literature searches were performed 94 on PubMed, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts 95 of Reviews of Effects, Cochrane Central Register of Controlled Trials, and the World 96 Allergy Organization Journal, one relevant journal that is not included in PubMed. In 97 most cases, searches were limited to the years 1988 to the present, with no language 98 restrictions. Additional publications identified by the EP and others involved in the 99 review process were also included in the RAND review if and only if they met the RAND 100 criteria for inclusion. 101 RAND researchers screened all titles found through searches, or that were submitted by 102 the EP or NIAID. Screening criteria were established to facilitate the identification of 103 articles concerning definitions, diagnoses, prevention, treatment, management, and other 104 topics. Articles were included or excluded based on article type and study purpose as 105 follows: 106 ● Article type 107 ○ Included: original research or systematic reviews 108 ○ Excluded: background or contextual reviews; non-systematic reviews; 109 commentary; other types of articles 110 ● Study purpose 111 ○ Included: incidence/prevalence/natural history; diagnosis; 112 treatment/management/prevention 113 ○ Excluded: not about food allergy; about some aspect not listed in the 114 “included” category 115 RAND screened over 12,300 titles, reviewed over 1,200 articles, abstracted nearly 116 900 articles, and included more than 200 articles in the final RAND report. Two RAND 117 investigators independently reviewed all titles and abstracts to identify potentially 118 relevant articles. Articles that met inclusion criteria were independently abstracted by a 119 single RAND investigator. Because of the large number of articles and the short time for 120 the review, articles were not independently abstracted by two RAND investigators 121 (dual-abstracted). However, team members worked together closely and data were 122 double-checked. A concise version of the report will be published in a peer-reviewed 123 journal and the full version of the report with a complete list of references will be made 124 available to the public shortly afterwards. 125 1.2.4 ASSESSING THE QUALITY AND STRENGTH OF THE BODY OF 126 EVIDENCE 127 For each key question, in addition to assessing the quality of each of the included studies, 128 RAND assessed the quality of the body of evidence using the Grading of 129 Recommendations Assessment, Development and Evaluation (GRADE) approach, which 130 was developed in 2004. GRADE provides a comprehensive and transparent methodology 131 for grading the quality of evidence and strength of recommendations about the diagnosis, 132 treatment, and management of patients. Using the GRADE approach, RAND assessed the 3 133 overall quality