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Practice parameter
Food allergy: a practice parameter
Chief Editors: Jean A. Chapman, MD; I. Leonard Bernstein, MD; Rufus E. Lee, MD;John Oppenheimer, MD; Associate Editors: Richard A. Nicklas, MD; Jay M. Portnoy, MD;Scott H. Sicherer, MD; Diane E. Schuller, MD; Sheldon L. Spector, MD; David Khan, MD;David Lang, MD; Ronald A. Simon, MD; Stephen A. Tilles, MD; Joann Blessing-Moore, MD;Dana Wallace, MD; and Suzanne S. Teuber, MD
TABLE OF CONTENTS
I. Preface.................................................................................................................................................................................S1II. Glossary...............................................................................................................................................................................S2III. Executive Summary............................................................................................................................................................S3IV. Summary Statements ..........................................................................................................................................................S6V. Classification of Major Food Allergens and Clinical Implications................................................................................S11VI. Mucosal Immune Responses Induced by Foods..............................................................................................................S12VII. The Clinical Spectrum of Food Allergy..........................................................................................................................S15VIII. Algorithm and Annotations..............................................................................................................................................S18IX. Prevalence and Epidemiology..........................................................................................................................................S21X. Natural History of Food Allergy......................................................................................................................................S22XI. Risk Factors and Prevention of Food Allergy.................................................................................................................S23XII. Cross-reactivity of Food Allergens..................................................................................................................................S24XIII. Adverse Reactions to Food Additives..............................................................................................................................S30XIV. Genetically Modified Foods.............................................................................................................................................S32XV. Diagnosis of Food Allergy...............................................................................................................................................S33XVI. Food-Dependent Exercise-Induced Anaphylaxis.............................................................................................................S39XVII. Differential Diagnosis of Adverse Reactions to Foods...................................................................................................S40XVIII. General Management of Food Allergy............................................................................................................................S44XIX. Management in Special Settings and Circumstances......................................................................................................S45XX. Future Directions ..............................................................................................................................................................S47XXI. Appendix: Suggested Oral Challenge Methods...............................................................................................................S48XXII. Acknowledgments.............................................................................................................................................................S49XXIII. References.........................................................................................................................................................................S50
PREFACE
Food allergy, as defined for the purposes of this document, is acondition caused by an IgE-mediated reaction to a food sub-stance. Adverse reactions to foods may also occur due to non–IgE-mediated immunologic and nonimmunologic mechanisms.Representing an important subset of all adverse food reactions,food allergy is often misunderstood. However, because of im-portant new scientific information, its evaluation and manage-ment have changed substantially in recent years.The prevalence of potentially life-threatening food allergyto peanuts and tree nuts is increasing. This has resulted in anincreased awareness among the general public, leading topolicy changes in schools, eating establishments, and theairline industry. At the same time, diagnostic evaluation inpatients suspected of having food allergy has become both
Received and accepted for publication August 30, 2005.The American Academy of Allergy, Asthma and Immunology (AAAAI) andthe American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing
Food Allergy: A PracticeParameter 
.
This is a complete and comprehensive document at thecurrent time. These clinical guidelines are designed to assist clinicians byproviding a framework for the evaluation and treatment of patients andare not intended to replace a clinician’s judgment or establish a protocolfor all patients. Themedical environment is a changing environment andnot all recommendations will be appropriate for all patients.
Because thisdocument incorporated the efforts of many participants, no single individual,including those who served on the Joint Task Force, is authorized to providean official AAAAI or ACAAI interpretation of these practice parameters.Any request for information about or an interpretation of these practiceparameters by the AAAAI or the ACAAI should be directed to theExecutive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters were developed bythe Joint Task Force on Practice Parameters, representing the AmericanAcademy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology, and the Joint Council of Allergy,Asthma and Immunology. These parameters are not designed for use bypharmaceutical companies in drug promotion. This parameter was editedby Dr Nicklas in his private capacity and not in his capacity as a medicalofficer with the Food and Drug Administration. No official support orendorsement by the Food and Drug Administration is intended or shouldbe inferred.VOLUME 96, MARCH, 2006 S1
 
more sophisticated and more challenging. The objective of Food Allergy: A Practice Parameter is to improve the care of patients by providing the practicing physician with an evi-dence-based approach to the diagnosis and management of IgE-mediated (allergic) food reactions. The Task Force rec-ognizes the importance of non–IgE-mediated immunologicand nonimmunologic food reactions and the role of the aller-gist-immunologist in their identification and management.These conditions are discussed in the context of differentialdiagnosis.This guideline was developed by the Joint Task Force onPractice Parameters, which has published 20 practice param-eters for the field of allergy-immunology (see list of publi-cations in the “Acknowledgments” section). The 3 nationalallergy and immunology societies—the American College of Allergy, Asthma and Immunology (ACAAI), the AmericanAcademy of Allergy, Asthma, and Immunology (AAAAI),and the Joint Council of Allergy, Asthma and Immunology(JCAAI)—have given the Joint Task Force the responsibilityfor both creating new parameters and updating existing pa-rameters. Although several previous parameters have ad-dressed the diagnosis and management of anaphylaxis, thisdocument is the first parameter that focuses on such reactionswith respect to foods. It was written and reviewed by spe-cialists in the field of allergy and immunology and wassupported by the 3 allergy and immunology organizationsnoted above.The working draft of this Food Allergy Practice Parameterwas prepared by the Joint Task Force on Practice Parameterswith the help of Scott Sicherer, MD. Preparation of this draftincluded a review of the medical literature using a variety of search engines such as PubMed. Published clinical studieswere rated by category of evidence and used to establish thestrength of a clinical recommendation (Table 1). The workingdraft of the Parameter was then reviewed by a number of experts on food allergy selected by the supporting organiza-tions. This document represents an evidence-based, broadlyaccepted consensus opinion.The Food Allergy Practice Parameter contains an anno-tated algorithm that presents the major decision points for theappropriate evaluation and management of patients suspectedof having food allergy. This is followed by summary state-ments, which represent the key points in the evaluation andmanagement of food allergies. These summary statementscan also be found before each section in this document,followed by text that supports the summary statement(s),which are, in turn, followed by graded references that supportthe statements in the text.The sections on diagnosis and management represent thecore of this practice parameter. The diagnosis section dis-cusses guidelines for establishing the diagnosis of food al-lergy and emphasizes the importance of obtaining a detailedhistory that is compatible with this diagnosis. There is also adetailed discussion of the appropriate use of skin prick orpuncture tests, serologic tests for specific IgE, and oral foodchallenges. The section on management discusses strategiesfor avoidance and guidelines for anticipating and implement-ing the medical treatment of food allergy reactions.In addition to the sections on diagnosis and management,this parameter includes sections on immunology of foodallergy, differential diagnosis, prevalence and epidemiology,natural history, risk factors, food allergens (including cross-reactivity), food additives, food-dependent exercise-inducedanaphylaxis (EIA), genetically modified foods, and manage-ment in specific circumstances (eg, schools).There are a number of objectives of this parameter on FoodAllergy, including (1) development of an improved under-standing of food allergy among health care professionals,medical students, interns, residents, and fellows, as well asmanaged care executives and administrators; (2) establish-ment of guidelines and support for the practicing physician;and (3) improvement in the quality of care for patients withfood allergy.
GLOSSARY
1. An
allergic epitope
denotes a specific peptide domainwithin a protein associated with allergenic potential.2.
Autotolerance
refers to the state of balance of the innateand adaptive immune systems in the gastrointestinal tract,whereby systemic immune responses to ingestants and com-mensal bacteria are prevented.3.
Class 1 Chitinases
are plant defense proteins. The aller-genic activity of plant Class 1 chitinases seems to be lost byheating.
Table 1. Classification of Evidence and Recommendations*Category of evidenceIa Evidence from meta-analysis of randomized controlled trialsIb Evidence from at least 1 randomized controlled trialIIa Evidence from at least 1 controlled study withoutrandomizationIIb Evidence from at least 1 other type of quasi-experimentalstudyIII Evidence from nonexperimental descriptive studies, such ascomparative studies, correlation studies, and case-controlledstudiesIV Evidence from expert committee reports or opinions or clinicalexperience of respected authorities, or bothLB Evidence from laboratory-based studies†Strength of recommendation A Directly based on category I evidenceB Directly based on category II evidence or extrapolated fromcategory I evidenceC Directly based on category III evidence or extrapolated fromcategory I or II evidenceD Directly based on category IV evidence or extrapolated fromcategory I, II or III evidenceE Directly based on category LB evidence†F Based on consensus of the Joint Task Force on PracticeParameters†* Adapted from Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Clin-ical guidelines: developing guidelines.
BMJ
. 1999;318:593–596.† Added by current authors.
S2 ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY
 
4. A
conformational epitope
consists of allergenic domainslocated at various noncontiguous amino acid regions of folded proteins.5.
In vitro assays to detect serum food specific IgE anti-body.
Modern in vitro detection systems generally do not useradioimmunoassay procedures (radioallergosorbent test[RAST]) but detect serum IgE by exposing serum to allergenbound to a solid matrix and using a secondary labeled (eg,fluorescent or enzyme-tagged) anti-IgE antibody to detect thebound IgE antibody. There are a variety of manufacturers,substrates, and manners of reporting results, including thePharmacia Unicap System, Diagnostic Products Corp,AlaSTAT, and Hycor Hy-Tech. These assays use a totalserum IgE heterologous reference curve based on a WorldHealth Organization IgE standard and quantitative results arereported in kIU/L.6.
Likelihood ratio
is the likelihood that a given test resultwould be expected in a patient with the disorder comparedwith the likelihood that the same result would be expected ina patient without the disorder.7.
Lipid transfer protein (LTP
) is a family of 9-kDapolypeptides, widely found in the vegetable kingdom andimplicated in cuticle formation and defense against patho-gens. They are thermostable and resistant to pepsin digestion,which makes them potent food allergens.8.
Mucosal adaptive immunity
refers to the unique andbidirectional abilities to confer protection against entericpathogens while providing tolerance to ingested foods andcommensal bacteria.9.
Oral food challenge.
A procedure during which poten-tially allergenic foods are gradually introduced through in-gestion, generally under physician supervision, often in a“blinded” and possibly placebo-controlled design to preventbias in interpretation, to observe for potential clinical reac-tions.10.
Panallergen
is a term that describes a homologousprotein with conserved IgE-binding epitopes across speciesthat cross-react with foods, plants, and pollen.11.
Percutaneous skin test 
(PST), such as prick or puncturetests, is a modality to identify food-specific IgE antibody byobserving a wheal-flare response after percutaneous introduc-tion of the allergen (commercial, or in some cases fresh,extract) into the skin by prick or puncture using a device suchas a lancet or other sharp instrument.12.
Phenylcoumarin benzylic ether reductase and isofla-vonoid reductase
are enzymes in the biosynthesis of plantlignans and isoflavonoids important in human health protec-tion (eg, for both the treatment and prevention of onset of various cancers) and in plant biology (eg, in defense func-tions and in tree heartwood development).13.
Predictive value
is the proportion of persons with apositive test result who have the disorder (positive predictivevalue) or the proportion of those with a negative test resultwithout the disorder (negative predictive value).14.
Profilins
are ubiquitous intracellular proteins highlycross-reactive among plant species and are one of severalidentified proteins responsible for cross-sensitivity amongplant pollen and food. Profilins are highly conserved proteinsin all eukaryotic organisms and are present in pollen and awide variety of vegetable foods.15.
Sensitivity and Specificity. Sensitivity
refers to theproportion of patients with a disorder who test positive, andspecificity is the proportion of individuals without a disorderwho have a negative test result.16.
Toll-like receptors
are human innate immune receptors.The designation of “toll” was adapted from homologousinnate immunity receptors originally discovered in
Drosoph-ila
species. Currently, there are 10 human toll-like receptors.17.
Transgenic foods
are foods that are genetically manip-ulated to contain insertions of foreign genetic DNAs selectedfor their ability to improve crop productivity or add nutri-tional value to the native food.18.
Tropomyosin
is a muscle protein that inhibits contrac-tion of a muscle by blocking the interaction of actin andmyosin.
EXECUTIVE SUMMARY
Adverse reactions to foods have been reported in up to 25%of the population at some point in their lives, with the highestprevalence observed during infancy and early childhood.Such reactions are generally divided on a basis of the under-lying pathophysiologic changes that produced the reaction,eg, food allergy, food intolerance, pharmacologic reactions,food poisoning, and toxic reactions (see the “DifferentialDiagnosis of Adverse Reactions to Foods” section). Althoughadverse reactions to foods are common, food allergy, definedfor the purposes of this document as an IgE-mediated re-sponse to a food, represents only a small percentage of alladverse reactions to foods. Individuals with atopy appearmore likely to develop food allergies compared with thegeneral population. Infants with moderate to severe atopicdermatitis appear to have the highest occurrence (see section“Prevalence and Epidemiology” section). In addition, chil-dren who develop an IgE-mediated reaction to one food are atgreater risk of developing IgE-mediated reactions to otherfoods and/or inhalants.Many studies indicate that the true prevalence of foodallergy is much lower than the number of suspected foodallergies. Therefore, health care professionals should not per-petuate false assumptions about food allergy. If a patient isincorrectly diagnosed as having a reaction to a food, unnec-essary dietary restrictions may adversely affect quality of life,nutritional status, and, in children, growth. Severely restricteddiets may lead to the development of eating disorders, espe-cially if they are used for prolonged periods, or may make thepatient susceptible to false claims of scientifically unprovenand often costly techniques that offer no actual benefit. Inaddition, unintentional exposure to foods falsely thought tocause adverse reactions can provoke unnecessary panic anduse of medications that have potentially potent adverse ef-fects.
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