Food allergy: A practice parameter update—2014

Abstract

This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology (JCAAI). The AAAAI and the ACAAI have jointly accepted responsibility for establishing “Food Allergy: A practice parameter update—2014.” This is a complete and comprehensive document at the current time. The medical environment is a changing one, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, ACAAI, and JCAAI. These parameters are not designed for use by pharmaceutical companies in drug promotion. This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology (JCAAI). The AAAAI and the ACAAI have jointly accepted responsibility for establishing “Food Allergy: A practice parameter update—2014.” This is a complete and comprehensive document at the current time. The medical environment is a changing one, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, ACAAI, and JCAAI. These parameters are not designed for use by pharmaceutical companies in drug promotion. Previously published practice parameters of the Joint Task Force on Practice Parameters for Allergy and Immunology are available at http://www.JCAAI.org or http://www.allergyparameters.org. The Joint Task Force has made a concerted effort to acknowledge all contributors to this parameter. If any contributors have been excluded inadvertently, the Task Force will ensure that appropriate recognition of such contributions is made subsequently. Hugh A. Sampson, MD Jaffe Food Allergy Institute Department of Pediatrics Icahn School of Medicine at Mount Sinai New York, New York Christopher Randolph Department of Pediatrics/Allergy/Immunology Yale Affiliated Hospitals Center for Allergy, Asthma, & Immunology Waterbury, Connecticut David I. Bernstein, MD Departments of Clinical Medicine and Environmental Health Division of Allergy/Immunology University of Cincinnati College of Medicine Cincinnati, Ohio Joann Blessing-Moore, MD Departments of Medicine and Pediatrics Stanford University Medical Center Department of Immunology Palo Alto, California David A. Khan, MD Department of Internal Medicine University of Texas Southwestern Medical Center Dallas, Texas David M. Lang, MD Allergy/Immunology Section Respiratory Institute Allergy and Immunology Fellowship Training Program Cleveland Clinic Foundation Cleveland, Ohio Richard A. Nicklas, MD Department of Medicine George Washington Medical Center Washington, DC John Oppenheimer, MD Department of Internal Medicine New Jersey Medical School Pulmonary and Allergy Associates Morristown, New Jersey Jay M. Portnoy, MD Section of Allergy, Asthma & Immunology Children's Mercy Hospital Department of Pediatrics University of Missouri–Kansas City School of Medicine Kansas City, Missouri Diane E. Schuller, MD Department of Pediatrics Pennsylvania State University Milton S. Hershey Medical College Hershey, Pennsylvania Sheldon L. Spector, MD Department of Medicine UCLA School of Medicine Los Angeles, California Stephen A. Tilles, MD Department of Medicine University of Washington School of Medicine Redmond, Washington Dana Wallace, MD Department of Medicine Nova Southeastern University College of Osteopathic Medicine Davie, Florida Seema Aceves, MD, PhD Eosinophilic Gastrointestinal Disorders Clinic Division of Allergy, Immunology Departments of Pediatrics and Medicine University of California, San Diego Rady Children's Hospital San Diego, California S. Allan Bock, MD Department of Pediatrics National Jewish Health Denver, Colorado Department of Pediatrics University of Colorado School of Medicine Aurora, Colorado John M. James, MD Private Clinical Practice Colorado Allergy and Asthma Centers, PC Fort Collins, Colorado Stacie Jones, MD Department of Pediatrics Allergy and Immunology University of Arkansas for Medical Sciences Arkansas Children's Hospital Little Rock, Arkansas David M. Lang, MD Allergy/Immunology Section Division of Medicine Allergy and Immunology Fellowship Training Program Cleveland Clinic Foundation Cleveland, Ohio Kari Nadeau, MD, PhD Department of Allergy, Asthma and Immunology Stanford University School of Medicine Stanford, California Anna Nowak-Wegrzyn, MD Department of Pediatrics Jaffe Food Allergy Institute Division of Allergy and Immunology Icahn School of Medicine at Mount Sinai New York, New York John Oppenheimer, MD Department of Internal Medicine New Jersey Medical School Pulmonary and Allergy Associates Morristown, New Jersey Tamara T. Perry, MD Department of Pediatrics Allergy and Immunology Division University of Arkansas for Medical Sciences Arkansas Children's Hospital Little Rock, Arkansas Scott H. Sicherer, MD Department of Pediatrics Pediatric Allergy and Immunology Icahn School of Medicine at Mount Sinai Jaffe Food Allergy Institute New York, New York Ronald A. Simon, MD Division of Allergy, Asthma & Immunology Scripps Clinic Department of Experimental & Molecular Medicine Scripps Research Institute La Jolla, California Brian P. Vickery, MD Department of Pediatrics University of North Carolina School of Medicine Chapel Hill, North Carolina Robert Wood, MD Department of Pediatrics and International Health Division of Pediatric Allergy and Immunology Johns Hopkins University School of Medicine Baltimore, Maryland I.Classification of major food allergens, cross-reactivities, genetically modified foods, and clinical implicationsA.ClassificationB.Cross-reactivityC.Genetically modified organisms in foods and the potential for allergenicityII.Mucosal immune responses induced by foodsIII.The clinical spectrum of food allergyA.Categories of adverse food reactionsB.Definitions of specific food-induced allergic conditionsIV.Prevalence, natural history, and preventionA.Natural historyB.Prevention of food allergyV.Adverse reactions to food additivesVI.Diagnosis of food allergy, differential diagnosis, and diagnostic algorithmA.Diagnosis of IgE-mediated food allergyB.Non-IgE mediated: FPIES, allergic proctocolitis, and enteropathyC.Eosinophilic esophagitisD.Eosinophilic gastroenteritisVII.Management of food allergy and food-dependent, exercise-induced anaphylaxisVIII.Emerging therapies for food allergyIX.Management in special settings Tabled 1StatementDefinitionImplicationStrong recommendation (StrRec)A strong recommendation means the benefits of the recommended approach clearly exceed the harms (or that the harms clearly exceed the benefits in the case of a strong negative recommendation) and that the quality of the supporting evidence is excellent (grade A or B).* In some clearly identified circumstances, strong recommendations might be made based on lesser evidence when high-quality evidence is impossible to obtain and the anticipated benefits strongly outweigh the harms.Clinicians should follow a strong recommendation unless a clear and compelling rationale for an alternative approach is present.Moderate (Mod)A recommendation means the benefits exceed the harms (or that the harms exceed the benefits in the case of a negative recommendation), but the quality of evidence is not as strong (grade B or C).* In some clearly identified circumstances, recommendations might be made based on lesser evidence when high-quality evidence is impossible to obtain and the anticipated benefits outweigh the harms.Clinicians should also generally follow a recommendation but should remain alert to new information and sensitive to patient preferences.Weak (Weak)An option means that either the quality of evidence that exists is suspect (grade D)* or that well-done studies (grade A, B, or C)* show little clear advantage to one approach versus another.Clinicians should be flexible in their decision making regarding appropriate practice, although they might set bounds on alternatives; patient preference should have a substantial influencing role.No recommendation (NoRec)No recommendation means there is both a lack of pertinent evidence (grade D)* and an unclear balance between benefits and harms.Clinicians should feel little constraint in their decision making and be alert to new published evidence that clarifies the balance of benefit versus harm; patient preference should have a substantial influencing role. Open table in a new tab IaEvidence from meta-analysis of randomized controlled trialsIbEvidence from at least 1 randomized controlled trialIIaEvidence from at least 1 controlled study without randomizationIIbEvidence from at least 1 other type of quasiexperimental studyIIIEvidence from nonexperimental descriptive studies, such as comparative studiesIVEvidence from expert committee reports or opinions or clinical experience of respected authorities or both ADirectly based on category I evidenceBDirectly based on category II evidence or extrapolated recommendation from category I evidenceCDirectly based on category III evidence or extrapolated recommendation from category I or II evidenceDDirectly based on category IV evidence or extrapolated recommendation from category I, II, or III evidenceLBLaboratory basedNRNot rated The following is a summary of interests disclosed on workgroup members' conflict of interest disclosure statements (not including information concerning family member interests). Completed conflict of interest disclosure statements are available on request.Tabled 1Work group memberDisclosuresHugh A. Sampson, MDAllertein Therapeutics – ConsultantFood Allergy Research and Education (FARE) – Medical Advisory Board, unpaidNovartis – Consultant, unpaidDBV Scientific Advisory Board, unpaidThermo Fisher Scientific – EAACI travel expenses and honorariumUCB – XX National Congress of the Mexican Pediatric Specialists in Clinical Immunology and Allergy – Travel expenses and honorariumNational Institute of Allergy and Infectious Diseases (NIAID) – Research grantFARE – Research grantUniversity of Nebraska (FARRP) – ConsultantAllergy and Asthma Foundation of America – ConsultantSeema Aceves, MD, PhDMeritage Pharma – Patent royaltiesS. Allan Bock, MDFood Allergy and Anaphylaxis Network — Medical Advisory BoardNational Jewish Health – Research affiliateJohn James, MDAmerican Board of Allergy and Immunology – Medical Advisory BoardParents of Asthmatic and Allergic Children – Medical Advisory BoardStacie Jones, MDNational Institutes of Health (NIH)/NIAID – Research grantNational Peanut Board – Research grantFARE – Advisory board; research grantSanofi-Aventis – Steering Committee MemberNIAID Safety Monitoring Committee – Grant reviewNIAID Study Section – Ad Hoc ReviewAAAAI – SpeakerIndiana University Medical School and Riley Children's Hospital – SpeakerSpanish Society of Allergy & Clinical Immunology (SEAIC), Madrid, Spain – SpeakerOregon Allergy, Asthma & Immunology Society – SpeakerDavid Lang, MDTera – SpeakerSanofi-Aventis – Advisory BoardMerck – Advisory Board; speakerAstra-Zeneca – SpeakerGenentech – SpeakerGlaxoSmithKline – SpeakerGenentech/Novartis – Research grantKari Nadeau, MD, PhDNIAID – Research grantFARE – Research grantAnna Nowak-Wegrzyn, MDMerck – Advisory BoardFARE – GrantNestle – GrantNew York Allergy and Asthma Society – Executive Committee MemberJohn Oppenheimer, MDTamara T. Perry, MDNIH/NHLBI – Research grantNIH/NIAID – Research grantNIH National Center for Minority Health Disparities – Research grantAR Center for Clinical and Translation Research – Research grantChristopher Randolph, MDGlaxoSmithKline – Consultant; speaker; honorarium; research grantAstra – Consultant; Advisory Board; speaker; honorarium; research grantMerck - Consultant; speaker; honorarium; research grantGenentech/Novartis - Consultant; speaker; honorarium; research grantBaxter – SpeakerDyax – Research grantDey – SpeakerAlcon - Speaker; honorarium; research grantISTA (Bepreve) – Speaker; honorariumSunovion (Sepracor) – SpeakerCSF Behring – SpeakerPharmaxis – Provided advertisementTEVA – Speaker; research grantConnecticut Allergy Society – OfficerScott H. Sicherer, MDAmerican Academy of Pediatrics – OfficerAmerican Board of Allergy Immunology – Board MemberAAAAI – SpeakerJournal of Allergy and Clinical Immunology/JACI-In Practice – Associate EditorNIH/NIAID – GrantsFARE – ConsultantFood Allergy Research and Education – Medical advisor/consultantNovartis - ConsultantRonald A. Simon, MDNovartis – Speakers' bureauNovartis – Research supportMerck – Speakers' bureauGlaxoSmithKline – Speakers' bureauBrian P. Vickery, MDCephalon – Research grantThrasher Research Fund – Research grantWallace Research Foundation – Research grantAmerican College of Allergy, Asthma & Immunology – GrantAmerican Lung Association – Grant/Steering Committee MemberNIH/NIAID – GrantRobert Wood, MDFARE — Medical Advisory BoardAllergy and Asthma Foundation of America – ConsultantNIH – Research supportAmerican Board of Allergy and Immunology – Board of DirectorsAmerican Board of Pediatrics – Board of DirectorsAmerican Academy of Allergy, Asthma & Immunology (AAAAI) – Board of Directors Open table in a new tab The Joint Task Force recognizes that experts in a field are likely to have interests that could come into conflict with development of a completely unbiased and objective practice parameter. A process has been developed to prevent potential conflicts from influencing the final document in a negative way to take advantage of that expertise. At the workgroup level, members who have a potential conflict of interest either do not participate in discussions concerning topics related to the potential conflict, or if they do write a section on that topic, the workgroup completely rewrites it without their involvement to remove potential bias. In addition, the entire document is reviewed by the Joint Task Force, and any apparent bias is removed at that level. Finally, the practice parameter is sent for review both by invited reviewers and by anyone with an interest in the topic by posting the document on the Web sites of the ACAAI and AAAAI. The practice parameter on food allergy was last updated in 20061American College of Allergy Astham & Immunology. Food allergy: a practice parameter.Ann Allergy Asthma Immunol. 2006; 96 (IV): S1-S68PubMed Google Scholar and focused primarily on IgE-mediated food allergy. In the ensuing years, there have been considerable advances in the field in many areas, including our basic understanding of food allergens, diagnostic testing, non–IgE-mediated disorders, and management of various food-induced allergic reactions. In 2010, the NIAID “Guidelines on the diagnosis and management of food allergy” were published, providing a comprehensive review of the scientific literature and expert opinion on food allergy.2Boyce J.A. Assa'ad A. Burks A.W. 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 (IV): S1-S58PubMed Google Scholar Given the many advances in the field, the Joint Task Force on Practice Parameters appointed a working group to review and update the standing practice parameters. The working group relied heavily on the NIAID Guidelines and focused on advances since the publication of that landmark document. The Joint Task Force on Practice Parameters (JTF) is a 13-member task force consisting of 6 representatives assigned by the AAAAI, 6 by the ACAAI, and 1 by the Joint Council of Allergy and Immunology. This task force oversees the development of practice parameters, selects the workgroup chair or chairs, and reviews drafts of the parameters for accuracy, practicality, clarity, and broad utility of the recommendations for clinical practice. The Food Allergy: A Practice Parameter Update 2014 Workgroup was commissioned by the JTF to develop a practice parameter that addresses recent advances in the field of food allergy and the optimal methods of diagnosis and management based on an assessment of the most current literature. The Chair (Hugh A. Sampson, MD) invited workgroup members to participate in the parameter development who are considered to be experts in the field of food allergy. Workgroup members have been vetted for financial conflict of interest by the JTF, and their conflicts of interest have been listed in this document and are posted on the JTF Web site at http://www.allergyparameters.org. The charge to the workgroup was to use a systematic literature review in conjunction with consensus expert opinion and workgroup-identified supplementary documents to develop a practice parameter that evaluates the current state of the science regarding food allergy. The NIAID guidelines were used to identify previously identified impactful studies on these topics. Additional Clinical reports were reviewed to ensure parity of expert opinion (AAP and ICON). Additional PubMed searches were performed primarily to identify items in the literature after September 2009 that were pertinent to update these topics. Meta-analyses were always selected when available. Grading of each reference was performed as applicable (see the reference list), and overall grades and strengths of recommendations were placed after the summary statements. Search terms include food allergy, food allergen, and each of the specific conditions reviewed in this parameter. Summary Statement 1: Evaluate the patient for possible food allergy with the understanding that a relatively small number of allergens cause a high proportion of food allergy (eg, cow's milk, hen's egg, soy, wheat, peanut, tree nuts, fish, and shellfish). See Summary Statement 48 for management. [Strength of recommendation: Strong; B Evidence] Summary Statement 2: Advise patients who are allergic to certain specific foods about the risk of ingestion of similar cross-reacting foods. Examples include ingestion of other tree nuts in patients with tree nut allergy (eg, walnut and pecan or pistachio and cashew), Crustacea in patients with crustacean seafood allergy, vertebrate fish in patients with fish allergy, and other mammalian milks in patients with cow's milk allergy. [Strength of recommendation: Strong; C Evidence] Summary Statement 3: Avoid other mammalian milks, such as goat's milk or sheep's milk, in patients with cow's milk allergy because of highly cross-reactive allergens. [Strength of recommendation: Strong; B Evidence] Summary Statement 4: Advise patients with seafood allergy that they are not at increased risk of a reaction to radiocontrast media. There is no documented relationship between non–IgE-mediated anaphylactic reactions to radiocontrast media and allergy to fish, crustacean shellfish, or iodine. [Strength of recommendation: Strong; D Evidence] Summary Statement 5: Test for IgE antibodies specific for the immunogenic oligosaccharide galactose-alpha-1, 3-galactose (alpha-gal) in patients who report a delayed systemic reaction to red meat or unexplained anaphylaxis, particularly if they have a history of previous tick bites. [Strength of recommendation: Moderate; C Evidence] Summary Statement 6: Avoid all mammalian meats in patients with alpha-gal allergy because this oligosaccharide antigen is widely expressed in mammalian tissues. [Strength of recommendation: Moderate; C Evidence] Summary Statement 7: Evaluate patients with latex allergy for the possibility of cross-reactivity to banana, avocado, kiwi, chestnut, potato, green pepper, and other fruits and nuts. Individualized management is recommended because clinical reactions caused by this cross-reactivity can range from mild to severe. [Strength of recommendation: Strong; C Evidence] Summary Statement 8: Advise patients not to be concerned about ingesting genetically modified foods given the current state of knowledge and the US Food and Drug Administration's screening requirements to rule out allergenicity of genetically modified foods. [Strength of recommendation: Weak; D Evidence] Summary Statement 9: Manage non–IgE-mediated reactions to foods with appropriate avoidance and pharmacotherapy as indicated with the understanding that the specific role of immunity (eg, IgA, IgM, IgG, and IgG subclasses) in these forms of food allergy has not been demonstrated. [Strength of recommendation: Strong; B Evidence] Summary Statement 10: Determine whether the reported history of food allergy, which often proves inaccurate, and laboratory data are sufficient to diagnose food allergy or whether an oral food challenge (OFC) is necessary. [Strength of recommendation: Strong; A Evidence] Summary Statement 11: Consider the natural course of allergies to specific foods when deciding on the frequency of food allergy follow-up evaluations, recognizing that allergies to certain foods (milk, egg, wheat, and soy) generally resolve more quickly in childhood than others (peanut, tree nuts, fish, and shellfish). These observations could support individualized follow-up (ie, roughly yearly re-evaluations of these allergies in childhood) with less frequent retesting if results remain particularly high (eg, >20-50 kUA/L). [Strength of recommendation: Moderate; C Evidence] Summary Statement 12: Encourage exclusive breast-feeding for the first 4 to 6 months of life. [Strength of recommendation: Weak; C Evidence] Summary Statement 13: For infants with a family history of atopy, consider a partially or extensively hydrolyzed infant formula for possible prevention of atopic dermatitis and infant cow's milk allergy if exclusive breast-feeding is not possible. [Strength of recommendation: Moderate; B Evidence] Summary Statement 14: Do not recommend maternal allergen avoidance or avoidance of specific complementary foods at weaning because these approaches have not proved effective for primary prevention of atopic disease. [Strength of recommendation: Weak; C Evidence] Summary Statement 15: Do not routinely recommend supplementation of the maternal or infant diet with probiotics or prebiotics as a means to prevent food allergy because there is insufficient evidence to support a beneficial effect. [Strength of recommendation: Weak; C Evidence] Summary Statement 16: Do not routinely recommend that patients with chronic idiopathic urticaria (CIU) avoid foods containing additives. [Strength of recommendation: Strong; B Evidence] Summary Statement 17: Do not routinely instruct asthmatic patients to avoid sulfites or other food additives unless they have a prior reaction to sulfites. Sulfites are the only food additive proved to trigger asthma. Although these reactions can be severe, even life-threatening in sensitive subjects, they are rare. [Strength of recommendation: Strong; B Evidence] Summary Statement 18: Consider natural food additives in the evaluation of patients with a history of unexplained ingestant-related anaphylaxis. [Strength of recommendation: Moderate; C Evidence] Summary Statement 19: Patients who experience an adverse reaction to food additives should be evaluated for sensitivity to annatto and carmine. [Strength of recommendation: Strong; A Evidence] Summary Statement 20: Clinicians should be aware that avoidance measures are appropriate for patients with histories compatible with adverse reactions to an additive until diagnostic evaluation can be performed. [Strength of recommendation: Moderate; C Evidence] Summary Statement 21: Clinicians should not recommend food additive avoidance in their patients with hyperactivity/attention deficit disorder. [Strength of recommendation: Strong; A Evidence] Summary Statement 22: The clinician should obtain a detailed medical history and physical examination to aid in the diagnosis of food allergy. [Strength of recommendation: Strong; D Evidence] Summary Statement 23: The clinician should use specific IgE tests (skin prick tests, serum tests, or both) to foods as diagnostic tools; however, testing should be focused on foods suspected of provoking the reaction, and test results alone should not be considered diagnostic of food allergy. [Strength of recommendation: Strong; B Evidence] Summary Statement 24: Component-resolved diagnostic testing to food allergens can be considered, as in the case of peanut sensitivity, but it is not routinely recommended even with peanut sensitivity because the clinical utility of component testing has not been fully elucidated. [Strength of recommendation: Weak; C Evidence] Summary Statement 25: The clinician should consider OFCs to aid in the diagnosis of IgE-mediated food allergy. [Strength of recommendation: Strong; A Evidence] Summary Statement 26: If clinical history is not consistent with anaphylaxis, perform a graded OFC to rule out food allergy. Open food challenge is both cost- and time-efficient. [Strength of recommendation: Moderate; C Evidence] Summary Statement 27: If the diagnosis is still unclear after open food challenge, then recommend a blind food challenge. [Strength of recommendation: Moderate; B Evidence] Summary Statement 28: Elimination diets and diet diaries can be used as an adjunctive means to diagnose food allergies but are not to be depended on solely for confirming a diagnosis. [Strength of recommendation: Weak; D Evidence] Summary Statement 29: A diagnosis of food-dependent, exercise-induced anaphylaxis should be considered when ingestion of causal food or foods and temporally related exercise result in symptoms of anaphylaxis. The clinician should recognize that symptoms only occur with ingestion of the causal food or foods proximate to exercise and that ingestion of the food in the absence of exercise will not result in anaphylaxis. [Strength of recommendation: Strong; B Evidence] Summary Statement 30: The clinician should consider the diagnosis of oral allergy syndrome (pollen-food allergy) and obtain specific IgE testing to pollens in patients who experience limited oropharyngeal symptoms after ingestion of food antigens that cross-react with pollen antigens. [Strength of recommendation: Strong; B Evidence] Summary Statement 31: A diagnosis of IgE-mediated contact urticaria should be considered in patients with a history of immediate urticarial rash at the site of contact with a food allergen. [Strength of recommendation: Weak; D Evidence] Summary Statement 32: Do not routinely obtain total serum IgE levels for the diagnosis of food allergy. [Strength of recommendation: Strong; C Evidence] Summary Statement 33: Do not perform intracutaneous testing for the diagnosis of food allergy (see discussion). [Strength of recommendation: Strong; B Evidence] Summary Statement 34: Unproved tests, including allergen-specific IgG measurement, cytotoxicity assays, applied kinesiology, provocation neutralization, and hair analysis, should not be used for the evaluation of food allergy. [Strength of recommendation: Strong; C Evidence] Summary Statement 35: Although routine use of atopy patch tests for diagnosis of food allergy is not recommended, the use of food atopy patch tests in patients with pediatric eosinophilic esophagitis (EoE) have been demonstrated to be valuable in assessing potential food triggers. [Strength of recommendation: Moderate; C Evidence] Summary Statement 36: The physician should use the patient's medical history, response to a trial of elimination of the suspected food, and OFC to establish a diagnosis of food protein–induced enterocolitis syndrome (FPIES). However, when the history indicates that infants or children have experienced hypotensive episodes or multiple reactions to the same food, a diagnosis can be based on a convincing history and absence of symptoms when the causative food is eliminated from the diet. [Strength of recommendation: Strong; B Evidence] Summary Statement 37: The clinician should be aware that a gastrointestinal evaluation with endoscopy and biopsy is usually not required for the diagnosis of FPIES and allergic proctocolitis with symptoms that respond to elimination of the offending food and recur when the food is reintroduced into the diet. [Strength of recommendation: Weak; C Evidence] Summary Statement 38: Measurement of food-specific IgG and IgG4 antibodies in serum are not recommended for the diagnosis of non–IgE-mediated food-related allergic disorders. [Strength of recommendation: Strong; B Evidence] Summary Statement 39: A trial of twice daily protein pump inhibitor (PPI) therapy for 8 weeks before diagnostic testing for EoE is recommended to exclude gastroesophageal reflux disease (GERD) and PPI-responsive esophageal infiltration of eosinophils. [Strength of recommendation: Strong; C Evidence] Summary Statement 40: The diagnosis of EoE should be based on the presence of characteristic symptoms and endoscopic features and the presence of 15 or more eosinophils per high-power field quantified by a pathologist using hematoxylin