Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report

Abstract

Contents∗SECTION 1. INTRODUCTION 178 1.1. Overview 178 1.2. Relationship of the US Guidelines to other guidelines 179 1.3. How the Guidelines were developed 1791.3.1. The Coordinating Committee 1791.3.2. The Expert Panel 1791.3.3. The independent, systematic literature review and report 1791.3.4. Assessing the quality of the body of evidence 1791.3.5. Preparation of the draft Guidelines and Expert Panel deliberations 1791.3.6. Public comment period and draft Guidelines revision 179 1.4. Defining the strength of each clinical guideline 179 1.5. Summary 180SECTION 2. DEFINITIONS, PREVALENCE, AND EPIDEMIOLOGY OF FOOD ALLERGY 180 2.1. Definitions 1802.1.1. Definitions of food allergy, food, and food allergens 1802.1.2. Definitions of related terms 1802.1.3. Definitions of specific food-induced allergic conditions 181 2.2. Prevalence and epidemiology of food allergy 1812.2.1. Systematic reviews of the prevalence of food allergy 1812.2.2. Prevalence of allergy to specific foods, food-induced anaphylaxis, and food allergy with comorbid conditions 181SECTION 3. NATURAL HISTORY OF FOOD ALLERGY AND ASSOCIATED DISORDERS 182 3.1. Natural history of food allergy in children 182 3.2. Natural history of levels of allergen-specific IgE to foods in children 182 3.3. Natural history of food allergy in adults 182 3.4. Natural history of conditions that coexist with food allergy 1823.4.1. Asthma 1823.4.2. Atopic dermatitis 1823.4.3. Eosinophilic esophagitis 1823.4.4. Exercise-induced anaphylaxis 182 3.5. Risk factors for the development of food allergy 182 3.6. Risk factors for severity of allergic reactions to foods 182 3.7. Incidence, prevalence, and consequences of unintentional exposure to food allergens 182SECTION 4. DIAGNOSIS OF FOOD ALLERGY 183 4.1. When should food allergy be suspected? 183 4.2. Diagnosis of IgE-mediated food allergy 1834.2.1. Medical history and physical examination 1834.2.2. Methods to identify the causative food 1834.2.2.1. Skin prick test 1834.2.2.2. Intradermal tests 1834.2.2.3. Total serum IgE 1834.2.2.4. Allergen-specific serum IgE 1834.2.2.5. Atopy patch test 1844.2.2.6. Use of skin prick tests, sIgE tests, and atopy patch tests in combination 1844.2.2.7. Food elimination diets 1844.2.2.8. Oral food challenges 1844.2.2.9. Nonstandardized and unproven procedures 184 4.3. Diagnosis of non-IgE-mediated immunologic adverse reactions to food 1844.3.1. Eosinophilic gastrointestinal diseases 1844.3.2. Food protein-induced enterocolitis syndrome 1844.3.3. Food protein-induced allergic proctocolitis 1844.3.4. Food protein-induced enteropathy syndrome 1844.3.5. Allergic contact dermatitis 1844.3.6. Systemic contact dermatitis 184 4.4. Diagnosis of IgE-mediated contact urticaria 184SECTION 5. MANAGEMENT OF NONACUTE ALLERGIC REACTIONS AND PREVENTION OF FOOD ALLERGY 185 5.1. Management of individuals with food allergy 1855.1.1. Dietary avoidance of specific allergens in IgE-mediated food allergy 1855.1.2. Dietary avoidance of specific allergens in non-IgE-mediated food allergy 1855.1.3. Effects of dietary avoidance on associated and comorbid conditions, such as atopic dermatitis, asthma, and eosinophilic esophagitis 1855.1.4. Food avoidance and nutritional status 1855.1.5. Food labeling in food allergy management 1855.1.6. When to re-evaluate patients with food allergy 1855.1.7. Pharmacologic intervention for the prevention of food-induced allergic reactions 1855.1.7.1. IgE-mediated reactions 1855.1.7.2. Non-IgE-mediated reactions 1855.1.8. Pharmacologic intervention for the treatment of food-induced allergic reactions 1855.1.9. Immunotherapy for food allergy management 1855.1.9.1. Allergen-specific immunotherapy 1855.1.9.2. Immunotherapy with cross-reactive allergens 1855.1.10. Quality-of-life issues associated with food allergy 1855.1.11. Vaccinations in patients with egg allergy 1855.1.11.1. Measles, mumps, rubella, and varicella vaccine 1865.1.11.2. Influenza vaccine 1865.1.11.3. Yellow fever vaccine 1865.1.11.4. Rabies vaccines 186 5.2. Management of individuals at risk for food allergy 1865.2.1. Nonfood allergen avoidance in at-risk patients 1865.2.2. Dietary avoidance of foods with cross-reactivities in at-risk patients 1865.2.3. Testing of allergenic foods in patients at high risk prior to introduction 1865.2.4. Testing in infants and children with persistent atopic dermatitis 187 5.3. Prevention of food allergy 1875.3.1. Maternal diet during pregnancy and lactation 1875.3.2. Breast-feeding 1875.3.3. Special diets in infants and young children 1875.3.3.1. Soy infant formula versus cow's milk formula 1875.3.3.2. Hydrolyzed infant formulas versus cow's milk formula or breast-feeding 1875.3.4. Timing of introduction of allergenic foods to infants 187SECTION 6. DIAGNOSIS AND MANAGEMENT OF FOOD-INDUCED ANAPHYLAXIS AND OTHER ACUTE ALLERGIC REACTIONS TO FOODS 187 6.1. Definition of anaphylaxis 187 6.2. Diagnosis of acute, life-threatening, food-induced allergic reactions 187 6.3. Treatment of acute, life-threatening, food-induced allergic reactions 1876.3.1. First-line and adjuvant treatment for food-induced anaphylaxis 1876.3.2. Treatment of refractory anaphylaxis 1896.3.3. Possible risks of acute therapy for anaphylaxis 1896.3.4. Treatment to prevent biphasic or protracted food-induced allergic reactions 1896.3.5. Management of milder, acute food-induced allergic reactions in health care settings 189 6.4. Management of food-induced anaphylaxis 189APPENDIX A. PRIMARY AUTHOR AFFILIATIONS AND ACKNOWLEDGMENTS 190APPENDIX B. LIST OF ABBREVIATIONS 192∗Some numbered sections found in the Guidelines are not included in this Summary because they do not include a guideline recommendation or an “In summary” statement, or because the detailed information in the section was not suitable for a concise Summary.Section 1. Introduction1.1 OverviewFood allergy (FA) is an important public health problem that affects adults and children and may be increasing in prevalence. Despite the risk of severe allergic reactions and even death, there is no current treatment for FA: the disease can only be managed by allergen avoidance or treatment of symptoms. Moreover, the diagnosis of FA may be problematic, given that nonallergic food reactions, such as food intolerance, are frequently confused with FAs. Additional concerns relate to the differences in the diagnosis and management of FA in different clinical practice settings.Due to these concerns, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, working with more than 30 professional organizations, federal agencies, and patient advocacy groups, led the development of “best practice” clinical guidelines for the diagnosis and management of FA (henceforth referred to as the Guidelines).1Boyce J.A. Assa'ad A. Burks W.A. Jones S.M. Sampson H.A. Wood R.A. et al.Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel.J Allergy Clin Immunol. 2010; 126: S1-S58PubMed Google Scholar Based on a comprehensive review and objective evaluation of the recent scientific and clinical literature on FA, the Guidelines were developed by and designed for allergists/immunologists, clinical researchers, and practitioners in the areas of pediatrics, family medicine, internal medicine, dermatology, gastroenterology, emergency medicine, pulmonary and critical care medicine, and others.The Guidelines focus on diseases that are defined as FA (see section 2.1) and include both IgE-mediated reactions to food and some non-IgE-mediated reactions to food. The Guidelines do not discuss celiac disease, which is an immunologic non-IgE-mediated reaction to certain foods. Although this is an immune-based disease involving food, existing clinical guidelines for celiac disease will not be restated here.Finally, these Guidelines do not address the management of patients with FA outside of clinical care settings (for example, schools and restaurants) or the related public health policy issues. These issues are beyond the scope of this document.1.2 Relationship of the US Guidelines to other guidelines(Not summarized here; refer to Guidelines.)1.3 How the Guidelines were developed1.3.1 The Coordinating CommitteeNIAID established a Coordinating Committee (CC), whose members are listed in Appendix A of the Guidelines, to oversee the development of the Guidelines; review drafts of the Guidelines for accuracy, practicality, clarity, and broad utility of the recommendations in clinical practice; review the final Guidelines; and disseminate the Guidelines. The CC members were from 34 professional organizations, advocacy groups, and federal agencies, and each member was vetted for financial conflict of interest (COI) by NIAID staff.1.3.2 The Expert PanelThe CC convened an Expert Panel (EP) in March 2009 that was chaired by Joshua Boyce, MD (Brigham and Women's Hospital, Boston, Mass). Panel members were specialists from a variety of relevant clinical, scientific, and public health areas (see Acknowledgments). Each member was vetted for financial COI by NIAID staff and approved by the CC. The charge to the EP was to use an independent, systematic literature review, in conjunction with consensus expert opinion and EP-identified supplementary documents, to develop Guidelines that provide a comprehensive approach for diagnosing and managing FA based on the current state of the science.1.3.3 The independent, systematic literature review and reportRAND Corporation prepared an independent, systematic literature review and evidence report on the state of the science in FA. This work was supported by an NIAID contract awarded in September 2008. The contract's principal investigator was Paul G. Shekelle, MD, PhD, an internationally recognized expert in the fields of practice guidelines and meta-analysis. RAND screened more than 12,300 titles, reviewed more than 1,200 articles, abstracted nearly 900 articles, and included 348 articles in the final RAND report. The full version of the report with a complete list of references is available at http://www.rand.org/pubs/working_papers/WR757-1/.1.3.4 Assessing the quality of the body of evidenceIn addition to assessing the quality of each of the included studies, RAND assessed the quality of the body of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, which was developed in 2004. GRADE provides a comprehensive and transparent methodology to develop recommendations for the diagnosis, treatment, and management of patients. In assessing the body of evidence, GRADE considers study design and other factors, such as the precision, consistency, and directness of the data. Using this approach, GRADE then provides a grade of high, moderate, or low for the quality of the body of evidence.1.3.5 Preparation of the draft Guidelines and Expert Panel deliberationsAll 43 clinical recommendations drafted by the EP received 90% (or higher) agreement. Sections 3, 5, and 6 of the Guidelines also contain “In summary” statements. These statements are intended to provide health care professionals with significant information that did not warrant a recommendation, or are in place of a recommendation when the EP or the CC could not reach consensus. All “In summary” statements received 90% (or higher) agreement.1.3.6 Public comment period and draft Guidelines revisionThe draft Guidelines were posted to the NIAID Web site in March 2010 for a period of 60 days to allow for public review and comment. More than 550 comments were collected and reviewed by the CC, the EP, and NIAID. The EP revised the Guidelines in response to some of these comments. The final Guidelines were published in the December 2010 issue of the Journal of Allergy and Clinical Immunology and are publically available at www.jacionline.org.1.4 Defining the strength of each clinical guidelineThe EP has used the verb “recommends” or “suggests” in each clinical guideline. These words convey the strength of the guideline, defined as follows:•Recommend is used when the EP strongly recommended for or against a particular course of action.•Suggest is used when the EP weakly recommended for or against a particular course of action.1.5 SummaryThe Guidelines are intended to assist health care professionals in making appropriate decisions about patient care in the United States. The recommendations are not fixed protocols that must be followed. Health care professionals should take these Guidelines into account when exercising their clinical judgment. However, this guidance does not override their responsibility to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient, guardian, or caregiver. Clinical judgment on the management of individual patients remains paramount. Health care professionals, patients, and their families need to develop individual treatment plans that are tailored to the specific needs and circumstances of the patient. This document is intended as a resource to guide clinical practice and develop educational materials for patients, their families, and the public. It is not an official regulatory document of any government agency.Section 2. Definitions, prevalence, and epidemiology of food allergy2.1 Definitions2.1.1 Definitions of food allergy, food, and food allergensThe EP came to consensus on definitions used throughout the Guidelines.A food allergy is defined as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food.A food is defined as any substance—whether processed, semiprocessed, or raw—that is intended for human consumption, and includes drinks, chewing gum, food additives, and dietary supplements. Substances used only as drugs, tobacco products, and cosmetics (such as lip-care products) that may be ingested are not included.Food allergens are defined as those specific components of food or ingredients within food (typically proteins, but sometimes also chemical haptens) that are recognized by allergen-specific immune cells and elicit specific immunologic reactions, resulting in characteristic symptoms. Some allergens (most often from fruits and vegetables) cause allergic reactions primarily if eaten when raw. However, most food allergens can still cause reactions even after they have been cooked or have undergone digestion in the stomach and intestines. A phenomenon called cross-reactivity may occur when an antibody reacts not only with the original allergen, but also with a similar allergen. In FA, cross-reactivity occurs when a food allergen shares structural or sequence similarity with a different food allergen or aeroallergen, which may then trigger an adverse reaction similar to that triggered by the original food allergen. Cross-reactivity is common, for example, among different shellfish and different tree nuts.Food oils—such as soy, corn, peanut, and sesame—range from very low allergenicity (if virtually all of the food protein is removed in processing) to very high allergenicity (if little of the food protein is removed in processing).2.1.2 Definitions of related termsBecause individuals can develop allergic sensitization (as evidenced by the presence of allergen-specific IgE (sIgE)) to food allergens without having clinical symptoms on exposure to those foods, an sIgE-mediated FA requires both the presence of sensitization and the development of specific signs and symptoms on exposure to that food. Sensitization alone is not sufficient to define FA.These Guidelines generally use the term tolerate to denote a condition where an individual has either naturally outgrown an FA or has received therapy and no longer develops clinical symptoms following ingestion of the food. This ability to tolerate food does not distinguish between these 2 possible clinical states. Individuals may tolerate food only for a short term, perhaps because they have been desensitized by exposure to the food. Alternatively, they may develop long-term tolerance. The specific term tolerance is used in these Guidelines to mean that an individual is symptom free after consumption of the food or upon oral food challenge weeks, months, or even years after the cessation of treatment. The immunological mechanisms that underlie tolerance in humans are poorly understood.Although many different foods and food components have been recognized as food allergens, these Guidelines focus on only those foods that are responsible for the majority of observed adverse allergic or immunologic reactions. Moreover, foods or food components that elicit reproducible adverse reactions but do not have established or likely immunologic mechanisms are not considered food allergens. Instead, these non-immunologic adverse reactions are termed food intolerances. For example, an individual may be allergic to cow's milk (henceforth referred to as milk) due to an immunologic response to milk protein, or alternatively, that individual may be intolerant to milk due to an inability to digest the sugar lactose. In the former situation, milk protein is considered an allergen because it triggers an adverse immunologic reaction. Inability to digest lactose leads to excess fluid production in the gastrointestinal (GI) tract, resulting in abdominal pain and diarrhea. This condition is termed lactose intolerance, and lactose is not an allergen because the response is not immune based. It should be noted that the words tolerance and intolerance are unrelated terms, even though the spelling of the words implies that they are opposites.2.1.3 Definitions of specific food-induced allergic conditionsThe reader is referred to the Guidelines for the definitions of the following:•Food-induced anaphylaxis•GI food allergies and several specific syndromes–Immediate GI hypersensitivity–Eosinophilic esophagitis (EoE)–Eosinophilic gastroenteritis–Food protein-induced allergic proctocolitis (AP)–Food protein-induced enterocolitis syndrome (FPIES)–Oral allergy syndrome (OAS)•Cutaneous reactions to foods–Acute urticaria–Angioedema–The increase in atopic dermatitis (AD) symptoms–Allergic contact dermatitis–Contact urticaria•Respiratory manifestations•Heiner syndrome2.2 Prevalence and epidemiology of food allergyThe true prevalence of FA has been difficult to establish for several reasons.•Although more than 170 foods have been reported to cause IgE-mediated reactions, most prevalence studies have focused on only the most common foods.•The incidence and prevalence of FA may have changed over time, and many studies have indeed suggested a true rise in prevalence over the past 10 to 20 years.•Studies of FA incidence, prevalence, and natural history are difficult to compare because of inconsistencies and deficiencies in study design and variations in the definition of FA.2.2.1 Systematic reviews of the prevalence of food allergy(Not summarized here; refer to Guidelines.)2.2.2 Prevalence of allergy to specific foods, food-induced anaphylaxis, and food allergy with comorbid conditionsThe following is a summary of prevalence data for the most common food allergies and anaphylaxis:Peanut•Prevalence of peanut allergy in the United States is about 0.6% of the population.•Prevalence of peanut allergy in France, Germany, Israel, Sweden, and the United Kingdom varies between 0.06% and 5.9%.Tree nuts•Prevalence of tree nut allergy in the United States is 0.4% to 0.5% of the population.•Prevalence of tree nut allergy in France, Germany, Israel, Sweden, and the United Kingdom varies between 0.03% and 8.5%.Seafood•Prevalence rates in the United States are significantly lower for children than for adults: fish allergy, 0.2% for children vs 0.5% for adults; crustacean shellfish allergy, 0.5% vs 2.5%; any seafood allergy, 0.6% vs 2.8%.•Prevalence rates in the United States are higher for women than for men: crustacean shellfish allergy, 2.6% for women vs 1.5% for men; any fish, 0.6% vs 0.2%.Milk and hen's egg•In a Danish cohort, allergy to milk was confirmed in 2.2%. Of these, 54% had IgE-mediated allergy, and the remaining 46% were classified as non-IgE mediated.•In a Norwegian cohort, the prevalence of hen's egg (henceforth referred to as egg) allergy was estimated to be 1.6%, and most egg reactions were IgE mediated.Food-induced anaphylaxis•Several studies in the United States assessed the incidence of anaphylaxis related to food. These studies found wide differences in the rates (from 1/100,000 population to as high as 70/100,000 population) of hospitalization or emergency department visits for anaphylaxis, as assessed by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes or medical record review.•The proportion of anaphylaxis cases thought to be due to foods also varied between 13% and 65%, with the lowest percentages found in studies that used more stringent diagnostic criteria for anaphylaxis.The EP agreed that any estimate of the overall US incidence of anaphylaxis is unlikely to have utility because such an estimate fails to reflect the substantial variability in patient age, geographic distribution, criteria used to diagnose anaphylaxis, and the study methods used.Section 3. Natural history of food allergy and associated disordersThe EP reviewed the literature on the natural history of FA and summarized the available data for the most common food allergens in the United States: egg, milk, peanut, tree nuts, wheat, crustacean shellfish, and soy. Natural history data for fish allergy were unavailable as of the completion of the systematic literature review (September 2009). It should be noted that many published studies addressing the natural history of FA typically come from selected populations (for example, from a single clinic or hospital) that may not be representative of the general or community-based patient population with a specific FA condition. Thus, the findings of these studies may not necessarily be extrapolated to all patients with the condition.3.1 Natural history of food allergy in childrenIn summary: Most children with FA eventually will tolerate milk, egg, soy, and wheat; far fewer will eventually tolerate tree nuts and peanut. The time course of FA resolution in children varies by food and may occur as late as the teenage years. A high initial level of sIgE against a food is associated with a lower rate of resolution of clinical allergy over time.3.2 Natural history of levels of allergen-specific IgE to foods in childrenIn summary: For many patients, sIgE antibodies to foods appear within the first 2 years of life. Levels may increase or decrease; a decrease is often associated with the ability to tolerate the foods.3.3 Natural history of food allergy in adultsIn summary: FA in adults can reflect persistence of pediatric FAs (for example, milk, peanut, and tree nuts) or de novo sensitization to food allergens encountered after childhood. Although there is a paucity of data from US studies, FA that starts in adult life tends to persist.3.4 Natural history of conditions that coexist with food allergyIn summary: FA may coexist with asthma, AD, EoE, and exercise-induced anaphylaxis. In patients with asthma, the coexistence of FA may be a risk factor for severe asthma exacerbations. Moreover, food may be a trigger for exercise-induced anaphylaxis. Elimination of food allergens in sensitized individuals can improve symptoms of some comorbid conditions.3.4.1 AsthmaIn summary: Asthma and FA often coexist in pediatric and adult patients. FA is associated with severe asthma.3.4.2 Atopic dermatitisIn summary: AD and FA are highly associated. When tolerance develops to a food, the reintroduction of the food in the diet will not result in recurrence or worsening of the AD.3.4.3 Eosinophilic esophagitisIn summary: EoE is commonly associated with sensitization to foods. The natural history of EoE is that of a chronic condition that resolves spontaneously or with therapy, and then relapses. There are insufficient data to judge the impact of food sensitization on the natural history of EoE, and vice versa. Only retrospective data exist that support a beneficial effect of dietary changes on the histopathologic changes in the esophagus in EoE.3.4.4 Exercise-induced anaphylaxisIn summary: Exercise-induced anaphylaxis in adults is triggered by foods in about one third of patients and has a natural history marked by frequent recurrence of the episodes.3.5 Risk factors for the development of food allergyIn summary: Family history of atopy and the presence of AD are risk factors for the development of both sensitization to food and confirmed FA.3.6 Risk factors for severity of allergic reactions to foodsIn summary: The severity of allergic reactions to foods is multifactorial and variable. The severity of a reaction cannot be accurately predicted by the degree of severity of past reactions nor by the level of sIgE or the size of the wheal from the skin prick test (SPT). The factor most commonly identified with the most severe reactions is the coexistence of asthma.3.7 Incidence, prevalence, and consequences of unintentional exposure to food allergensIn summary: Self-reported reactions to food frequently occur in patients with a known diagnosis of FA. Although a subset of these reactions is due to intentional exposure, most are due to unintentional exposure. Both types of exposure can be life-threatening. There is no evidence that unintentional or intentional exposures to the food allergen alter the natural history of the FA.Section 4. Diagnosis of food allergy4.1 When should food allergy be suspected?Guideline 1: The EP recommends that FA should be considered:•In individuals presenting with anaphylaxis or any combination of symptoms listed in Table I that occur within minutes to hours of ingesting food, especially in young children and/or if symptoms have followed the ingestion of a specific food on more than 1 occasionTable ISymptoms of food-induced allergic reactionsTarget organImmediate symptomsDelayed symptomsCutaneousErythemaPruritusUrticariaMorbilliform eruptionAngioedemaErythemaFlushingPruritusMorbilliform eruptionAngioedemaEczematous rashOcularPruritusConjunctival erythemaTearingPeriorbital edemaPruritusConjunctival erythemaTearingPeriorbital edemaUpper respiratoryNasal congestionPruritusRhinorrheaSneezingLaryngeal edemaHoarsenessDry staccato coughLower respiratoryCoughChest tightnessDyspneaWheezingIntercostal retractionsAccessory muscle useCough, dyspnea, and wheezingGI (oral)Angioedema of the lips, tongue, or palateOral pruritusTongue swellingGI (lower)NauseaColicky abdominal painRefluxVomitingDiarrheaNauseaAbdominal painRefluxVomitingDiarrheaHematocheziaIrritability and food refusal with weight loss (young children)CardiovascularTachycardia (occasionally bradycardia in anaphylaxis)HypotensionDizzinessFaintingLoss of consciousnessMiscellaneousUterine contractionsSense of “impending doom”GI, Gastrointestinal.Note: This table is presented as Table IV in the Guidelines. Open table in a new tab •In infants, young children, and selected older children diagnosed with certain disorders, such as moderate to severe AD, EoE, enterocolitis, enteropathy, and allergic proctocolitis•In adults diagnosed with EoE4.2 Diagnosis of IgE-mediated food allergy4.2.1 Medical history and physical examinationGuideline 2: The EP recommends using medical history and physical examination to aid in the diagnosis of FA.•Medical history: The EP recommends using a detailed medical history to help focus the evaluation of an FA. Although the medical history often provides evidence for the type of food-induced allergic reaction and the potential causative food(s) involved, history alone cannot be considered diagnostic of FA.•Physical examination: The EP recommends performing a focused physical examination of the patient, which may provide signs consistent with an allergic reaction or disorder often associated with FA. However, by itself, the physical examination cannot be considered diagnostic of FA.Guideline 3: The EP recommends that parent and patient reports of FA must be confirmed, because multiple studies demonstrate that 50% to 90% of presumed FAs are not allergies.4.2.2 Methods to identify the causative food4.2.2.1 Skin prick testGuideline 4: The EP recommends performing an SPT (also known as a skin puncture test) to assist in the identification of foods that may be provoking IgE-mediated food-induced allergic reactions, but the SPT alone cannot be considered diagnostic of FA.4.2.2.2 Intradermal testsGuideline 5: The EP recommends that intradermal testing should not be used to make a diagnosis of FA.4.2.2.3 Total serum IgEGuideline 6: The EP recommends that the routine use of measuring total serum IgE should not be used to make a diagnosis of FA.4.2.2.4 Allergen-specific serum IgEGuideline 7: The EP recommends sIgE tests for identifying foods that potentially provoke IgE-mediated food-induced allergic reactions, but alone these tests are not diagnostic of FA.4.2.2.5 Atopy patch testGuideline 8: The EP suggests that the atopy patch test (APT) should not be used in the routine evaluation of non-contact FA.4.2.2.6 Use of skin prick tests, sIgE tests, and atopy patch tests in combinationGuideline 9: The EP suggests not using the combination of SPTs, sIgE tests, and APTs for the routine diagnosis of FA.4.2.2.7 Food elimination dietsGuideline 10: The EP suggests that elimination of 1 or a few specific foods from the diet may be useful in the diagnosis of FA, especially in identifying foods responsible for some non-IgE-mediated food-induced allergic disorders, such as FPIES, AP, and Heiner syndrome, and some mixed IgE- and non-IgE-mediated food-induced allergic disorders, such as EoE.4.2.2.8 Oral food challengesGuideline 11: The EP recommends using oral food challenges for diagnosing