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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.................................................................................................................................................................................S1 II. Glossary...............................................................................................................................................................................S2 III. Executive Summary............................................................................................................................................................S3 IV. Summary Statements..........................................................................................................................................................S6 V. Classification of Major Food Allergens and Clinical Implications................................................................................S11 VI. Mucosal Immune Responses Induced by Foods..............................................................................................................S12 VII. The Clinical Spectrum of Food Allergy..........................................................................................................................S15 VIII. Algorithm and Annotations..............................................................................................................................................S18 IX. Prevalence and Epidemiology..........................................................................................................................................S21 X. Natural History of Food Allergy......................................................................................................................................S22 XI. Risk Factors and Prevention of Food Allergy.................................................................................................................S23 XII. Cross-reactivity of Food Allergens..................................................................................................................................S24 XIII. Adverse Reactions to Food Additives..............................................................................................................................S30 XIV. Genetically Modified Foods.............................................................................................................................................S32 XV. Diagnosis of Food Allergy...............................................................................................................................................S33 XVI. Food-Dependent Exercise-Induced Anaphylaxis.............................................................................................................S39 XVII. Differential Diagnosis of Adverse Reactions to Foods...................................................................................................S40 XVIII. General Management of Food Allergy............................................................................................................................S44 XIX. Management in Special Settings and Circumstances......................................................................................................S45 XX. Future Directions..............................................................................................................................................................S47 XXI. Appendix: Suggested Oral Challenge Methods...............................................................................................................S48 XXII. Acknowledgments.............................................................................................................................................................S49 XXIII. References.........................................................................................................................................................................S50 PREFACE portant new scientific information, its evaluation and manage- menthavechangedsubstantiallyinrecentyears. Foodallergy,asdefinedforthepurposesofthisdocument,isa The prevalence of potentially life-threatening food allergy condition caused by an IgE-mediated reaction to a food sub- topeanutsandtreenutsisincreasing.Thishasresultedinan stance.Adversereactionstofoodsmayalsooccurduetonon– increased awareness among the general public, leading to IgE-mediated immunologic and nonimmunologic mechanisms. policy changes in schools, eating establishments, and the Representinganimportantsubsetofalladversefoodreactions, airline industry. At the same time, diagnostic evaluation in food allergy is often misunderstood. However, because of im- patients suspected of having food allergy has become both ReceivedandacceptedforpublicationAugust30,2005. Any request for information about or an interpretation of these practice TheAmericanAcademyofAllergy,AsthmaandImmunology(AAAAI)and parameters by the AAAAI or the ACAAI should be directed to the theAmericanCollegeofAllergy,AsthmaandImmunology(ACAAI)have Executive Offices of the AAAAI, the ACAAI, and the Joint Council of jointly accepted responsibility for establishing Food Allergy: A Practice Allergy,AsthmaandImmunology.Theseparametersweredevelopedby Parameter. This is a complete and comprehensive document at the theJointTaskForceonPracticeParameters,representingtheAmerican currenttime.Theseclinicalguidelinesaredesignedtoassistcliniciansby AcademyofAllergy,AsthmaandImmunology,theAmericanCollegeof providingaframeworkfortheevaluationandtreatmentofpatientsand Allergy, Asthma and Immunology, and the Joint Council of Allergy, arenotintendedtoreplaceaclinician’sjudgmentorestablishaprotocol AsthmaandImmunology.Theseparametersarenotdesignedforuseby forallpatients.Themedicalenvironmentisachangingenvironmentand pharmaceuticalcompaniesindrugpromotion.Thisparameterwasedited notallrecommendationswillbeappropriateforallpatients.Becausethis byDrNicklasinhisprivatecapacityandnotinhiscapacityasamedical documentincorporatedtheeffortsofmanyparticipants,nosingleindividual, officer with the Food and Drug Administration. No official support or includingthosewhoservedontheJointTaskForce,isauthorizedtoprovide endorsementbytheFoodandDrugAdministrationisintendedorshould an official AAAAI or ACAAI interpretation of these practice parameters. beinferred. VOLUME 96, MARCH, 2006 S1 more sophisticated and more challenging. The objective of Table1.ClassificationofEvidenceandRecommendations* FoodAllergy:APracticeParameteristoimprovethecareof Categoryofevidence patients by providing the practicing physician with an evi- Ia Evidencefrommeta-analysisofrandomizedcontrolledtrials dence-based approach to the diagnosis and management of Ib Evidencefromatleast1randomizedcontrolledtrial IgE-mediated (allergic) food reactions. The Task Force rec- IIa Evidencefromatleast1controlledstudywithout ognizes the importance of non–IgE-mediated immunologic randomization andnonimmunologicfoodreactionsandtheroleofthealler- IIb Evidencefromatleast1othertypeofquasi-experimental study gist-immunologist in their identification and management. III Evidencefromnonexperimentaldescriptivestudies,suchas These conditions are discussed in the context of differential comparativestudies,correlationstudies,andcase-controlled diagnosis. studies This guideline was developed by the Joint Task Force on IV Evidencefromexpertcommitteereportsoropinionsorclinical PracticeParameters,whichhaspublished20practiceparam- experienceofrespectedauthorities,orboth eters for the field of allergy-immunology (see list of publi- LB Evidencefromlaboratory-basedstudies† cations in the “Acknowledgments” section). The 3 national Strengthofrecommendation allergyandimmunologysocieties—theAmericanCollegeof A DirectlybasedoncategoryIevidence Allergy, Asthma and Immunology (ACAAI), the American B DirectlybasedoncategoryIIevidenceorextrapolatedfrom Academy of Allergy, Asthma, and Immunology (AAAAI), categoryIevidence C DirectlybasedoncategoryIIIevidenceorextrapolatedfrom and the Joint Council of Allergy, Asthma and Immunology categoryIorIIevidence (JCAAI)—havegiventheJointTaskForcetheresponsibility D DirectlybasedoncategoryIVevidenceorextrapolatedfrom for both creating new parameters and updating existing pa- categoryI,IIorIIIevidence rameters. Although several previous parameters have ad- E DirectlybasedoncategoryLBevidence† dressed the diagnosis and management of anaphylaxis, this F BasedonconsensusoftheJointTaskForceonPractice documentisthefirstparameterthatfocusesonsuchreactions Parameters† with respect to foods. It was written and reviewed by spe- *AdaptedfromShekellePG,WoolfSH,EcclesM,GrimshawJ.Clin- cialists in the field of allergy and immunology and was icalguidelines:developingguidelines.BMJ.1999;318:593–596. supported by the 3 allergy and immunology organizations †Addedbycurrentauthors. noted above. TheworkingdraftofthisFoodAllergyPracticeParameter waspreparedbytheJointTaskForceonPracticeParameters foravoidanceandguidelinesforanticipatingandimplement- withthehelpofScottSicherer,MD.Preparationofthisdraft ing the medical treatment of food allergy reactions. includedareviewofthemedicalliteratureusingavarietyof In addition to the sections on diagnosis and management, search engines such as PubMed. Published clinical studies this parameter includes sections on immunology of food were rated by category of evidence and used to establish the allergy, differential diagnosis, prevalence and epidemiology, strengthofaclinicalrecommendation(Table1).Theworking natural history, risk factors, food allergens (including cross- draft of the Parameter was then reviewed by a number of reactivity), food additives, food-dependent exercise-induced experts on food allergy selected by the supporting organiza- anaphylaxis (EIA), genetically modified foods, and manage- tions. This document represents an evidence-based, broadly ment in specific circumstances (eg, schools). accepted consensus opinion. ThereareanumberofobjectivesofthisparameteronFood The Food Allergy Practice Parameter contains an anno- Allergy, including (1) development of an improved under- tatedalgorithmthatpresentsthemajordecisionpointsforthe standing of food allergy among health care professionals, appropriateevaluationandmanagementofpatientssuspected medical students, interns, residents, and fellows, as well as of having food allergy. This is followed by summary state- managed care executives and administrators; (2) establish- ments, which represent the key points in the evaluation and ment of guidelines and support for the practicing physician; management of food allergies. These summary statements and (3) improvement in the quality of care for patients with can also be found before each section in this document, food allergy. followed by text that supports the summary statement(s), whichare,inturn,followedbygradedreferencesthatsupport GLOSSARY the statements in the text. 1. An allergic epitope denotes a specific peptide domain The sections on diagnosis and management represent the within a protein associated with allergenic potential. core of this practice parameter. The diagnosis section dis- 2.Autotolerancereferstothestateofbalanceoftheinnate cusses guidelines for establishing the diagnosis of food al- and adaptive immune systems in the gastrointestinal tract, lergy and emphasizes the importance of obtaining a detailed whereby systemic immune responses to ingestants and com- historythatiscompatiblewiththisdiagnosis.Thereisalsoa mensal bacteria are prevented. detailed discussion of the appropriate use of skin prick or 3.Class1Chitinasesareplantdefenseproteins.Thealler- puncture tests, serologic tests for specific IgE, and oral food genic activity of plant Class 1 chitinases seems to be lost by challenges. The section on management discusses strategies heating. S2 ANNALSOFALLERGY,ASTHMA&IMMUNOLOGY 4.Aconformationalepitopeconsistsofallergenicdomains identified proteins responsible for cross-sensitivity among located at various noncontiguous amino acid regions of plantpollenandfood.Profilinsarehighlyconservedproteins folded proteins. in all eukaryotic organisms and are present in pollen and a 5. In vitro assays to detect serum food specific IgE anti- wide variety of vegetable foods. body.Moderninvitrodetectionsystemsgenerallydonotuse 15. Sensitivity and Specificity. Sensitivity refers to the radioimmunoassay procedures (radioallergosorbent test proportion of patients with a disorder who test positive, and [RAST])butdetectserumIgEbyexposingserumtoallergen specificityistheproportionofindividualswithoutadisorder bound to a solid matrix and using a secondary labeled (eg, who have a negative test result. fluorescentorenzyme-tagged)anti-IgEantibodytodetectthe 16.Toll-likereceptorsarehumaninnateimmunereceptors. bound IgE antibody. There are a variety of manufacturers, The designation of “toll” was adapted from homologous substrates, and manners of reporting results, including the innateimmunityreceptorsoriginallydiscoveredinDrosoph- Pharmacia Unicap System, Diagnostic Products Corp, ilaspecies.Currently,thereare10humantoll-likereceptors. AlaSTAT, and Hycor Hy-Tech. These assays use a total 17.Transgenicfoodsarefoodsthataregeneticallymanip- serum IgE heterologous reference curve based on a World ulatedtocontaininsertionsofforeigngeneticDNAsselected HealthOrganizationIgEstandardandquantitativeresultsare for their ability to improve crop productivity or add nutri- reported in kIU/L. tional value to the native food. 6.Likelihoodratioisthelikelihoodthatagiventestresult 18. Tropomyosin is a muscle protein that inhibits contrac- would be expected in a patient with the disorder compared tion of a muscle by blocking the interaction of actin and withthelikelihoodthatthesameresultwouldbeexpectedin myosin. a patient without the disorder. 7. Lipid transfer protein (LTP) is a family of 9-kDa EXECUTIVE SUMMARY polypeptides, widely found in the vegetable kingdom and Adverse reactions to foods have been reported in up to 25% implicated in cuticle formation and defense against patho- gens.Theyarethermostableandresistanttopepsindigestion, ofthepopulationatsomepointintheirlives,withthehighest which makes them potent food allergens. prevalence observed during infancy and early childhood. 8. Mucosal adaptive immunity refers to the unique and Suchreactionsaregenerallydividedonabasisoftheunder- bidirectional abilities to confer protection against enteric lying pathophysiologic changes that produced the reaction, pathogens while providing tolerance to ingested foods and eg, food allergy, food intolerance, pharmacologic reactions, commensal bacteria. food poisoning, and toxic reactions (see the “Differential 9. Oral food challenge. A procedure during which poten- DiagnosisofAdverseReactionstoFoods”section).Although tially allergenic foods are gradually introduced through in- adversereactionstofoodsarecommon,foodallergy,defined gestion, generally under physician supervision, often in a for the purposes of this document as an IgE-mediated re- “blinded” and possibly placebo-controlled design to prevent sponse to a food, represents only a small percentage of all bias in interpretation, to observe for potential clinical reac- adverse reactions to foods. Individuals with atopy appear tions. more likely to develop food allergies compared with the 10. Panallergen is a term that describes a homologous general population. Infants with moderate to severe atopic protein with conserved IgE-binding epitopes across species dermatitisappeartohavethehighestoccurrence(seesection that cross-react with foods, plants, and pollen. “Prevalence and Epidemiology” section). In addition, chil- 11.Percutaneousskintest(PST),suchasprickorpuncture drenwhodevelopanIgE-mediatedreactiontoonefoodareat tests, is a modality to identify food-specific IgE antibody by greater risk of developing IgE-mediated reactions to other observingawheal-flareresponseafterpercutaneousintroduc- foods and/or inhalants. tion of the allergen (commercial, or in some cases fresh, Many studies indicate that the true prevalence of food extract)intotheskinbyprickorpunctureusingadevicesuch allergy is much lower than the number of suspected food as a lancet or other sharp instrument. allergies.Therefore,healthcareprofessionalsshouldnotper- 12. Phenylcoumarin benzylic ether reductase and isofla- petuate false assumptions about food allergy. If a patient is vonoid reductase are enzymes in the biosynthesis of plant incorrectly diagnosed as having a reaction to a food, unnec- lignans and isoflavonoids important in human health protec- essarydietaryrestrictionsmayadverselyaffectqualityoflife, tion (eg, for both the treatment and prevention of onset of nutritionalstatus,and,inchildren,growth.Severelyrestricted various cancers) and in plant biology (eg, in defense func- diets may lead to the development of eating disorders, espe- tions and in tree heartwood development). ciallyiftheyareusedforprolongedperiods,ormaymakethe 13. Predictive value is the proportion of persons with a patient susceptible to false claims of scientifically unproven positivetestresultwhohavethedisorder(positivepredictive and often costly techniques that offer no actual benefit. In value) or the proportion of those with a negative test result addition, unintentional exposure to foods falsely thought to without the disorder (negative predictive value). cause adverse reactions can provoke unnecessary panic and 14. Profilins are ubiquitous intracellular proteins highly use of medications that have potentially potent adverse ef- cross-reactive among plant species and are one of several fects. VOLUME 96, MARCH, 2006 S3 IgE-mediated reactions to food allergens may occur as a food-induced anaphylaxis, with those at greatest risk being consequence of (1) sensitization through the gastrointestinal adolescents with asthma. tract;(2)sensitizationthroughtherespiratorytracttoairborne On the other hand, allergy to fruits and vegetables, which proteins that are either identical (eg, occupational exposure) are the most common food allergies reported by adults, may or homologous to those in particular foods (see “Classifica- develop later in life as a consequence of shared homologous tion of Major Food Allergens and Clinical Implications” proteins with airborne allergens (eg, pollens). Why food section); or (3) sensitization through epidermis having im- allergy persists in some patients and not in others is unclear, paired barrier function. Characteristics of the proteins them- although recent studies suggest that this is more likely to selvesandtheparticulartypeanddegreeofimmuneresponse occur with foods that contain linear allergenic epitopes. that they elicit determine the clinical manifestations of the Risk factors associated with the development of food al- condition that results from patient exposure. Mucosal adap- lergy include a personal or family history of atopy or food tiveimmunityinthegastrointestinaltractisinfluencedbythe allergyinparticular,possiblematernalconsumptionofmajor nature and the dose of antigen, the immaturity of the host, food allergens during either pregnancy or breastfeeding, genetic susceptibility, the rate of absorption of a dietary atopicdermatitis,andtransdermalfoodexposure.Aninfantat protein, and the conditions of antigen processing (see “Mu- increased risk is a candidate for intervention, which may include breastfeeding and avoidance of highly sensitizing cosal Immune Responses Induced by Foods” section). Mo- and/or solid foods at a young age, to reduce this risk. lecular and immunologic techniques can provide data on Reactions that occur in individuals after the ingestion, whichallergensorepitopesofanallergeninaparticularfood inhalation, or contact with foods or food additives can vary may be responsible for specific clinical outcomes (see from mild, gradually developing symptoms limited to the “Cross-reactivityofFoodAllergens”section).IgEantibodies gastrointestinal tract to severe, rapidly progressing, life- maybedirectedtoavarietyofpotentialallergenicproteinsin threatening anaphylactic reactions that may be triggered by foods(eg,caseinandwheyproteinsincow’smilk,eggwhite evensmallamountsoffoodallergen.Immunologicreactions proteins in hen’s eggs, parvalbumin in finned fish, and tro- to foods or food additives are characterized by a strong pomyosin in shellfish). temporal relationship between the onset of the reaction and Immune responses to a particular allergen can vary, de- exposuretoaspecificfoodorfoodadditiveandmayinclude pending on the method of exposure and the condition of the cutaneousmanifestations,gastrointestinalsymptoms,respira- food.Forexample,thereareavarietyofimmuneresponsesto torysymptoms,hypotension,andlaryngealedema,occurring wheatthatinclude(1)acuteIgE-mediatedreactions,(2)local separately or together. inhalational reactions (baker’s asthma), (3) systemic reac- Anaphylaxis after exposure to foods can include a combi- tions that occur when wheat is ingested following exercise, nation of symptoms that reflect reactions in the respiratory, and(4)cell-mediatedreactionsinatopicdermatitisandceliac dermatologic, cardiovascular, and other organ systems. In disease.Patientswhoareallergictoeggproteinsmaybeable children, anaphylaxis occurs most frequently after ingestion to tolerate these allergens when eggs are processed as an ofpeanuts,otherlegumes,treenuts,fish,shellfish,milk,and ingredientinpreparedfoods.Cookingafoodmayincreaseor eggs. Most IgE-mediated reactions to foods in adults are decrease the patient’s ability to tolerate a food. caused by peanuts, tree nuts, fish, and shellfish. In highly Recent studies with molecular biological techniques have sensitive patients, inhalation of food allergens may produce characterized a variety of cross-reacting allergens among anaphylaxis. Anaphylaxis may also occur when foods are foods, including tropomyosins, bovine IgG, lipid transfer ingested before or after exercise (see “Food-Dependent Ex- protein, profilin, and chitinases. Although IgE cross-reactiv- ercise-Induced Anaphylaxis” section). ity to multiple foods is common, clinical correlation is often Immunologicreactionstofoodsencompassmorethanjust limited (see “Cross-reactivity of Food Allergens” section). IgE-mediated reactions. Nevertheless, this monograph will Although sensitivity to most food allergens, such as milk, focus primarily on IgE-mediated reactions that have been wheat,andegg,tendtoremitinlatechildhood,persistenceof definedforthepurposesofthisdocumentasfoodallergy.An other food allergies, eg, peanut, tree nut (walnut, cashew, IgE-mediatedreactiontofoodsmaybedifficulttodistinguish Brazil nut, pistachio), and seafood, are most likely to con- from other types of reactions to foods, such as food intoler- tinue throughout the patient’s life (see “Natural History of ance, especially if symptoms are primarily or exclusively FoodAllergy”section).Thenaturalhistoryofspecificfoods gastrointestinal (see “Differential Diagnosis of Adverse Re- variessubstantially.Forexample,childrenwhohavebecome actions to Foods” section). IgE-mediated reactions can also sensitized to cow’s milk, hen’s egg, wheat, and soybean occurintheupperandlowerrespiratorytract,usuallyaspart through the gastrointestinal tract will usually lose this sensi- of an anaphylactic reaction that may involve the skin and/or tivity as they get older. Peanut allergy, on the other hand, is gastrointestinal tract. In IgE-mediated reactions (1) the time usually not lost as the patient gets older, with only approxi- fromingestionofthefoodtosymptomonsetisusuallyrapid mately 20% of children with peanut allergy losing this sen- (eg, within minutes), (2) small amounts of food may elicit sitivity. Peanut allergy affects approximately 0.6% of the severe reactions, and (3) reactions will usually continue to general population and is the most common cause of fatal occurwithreexposure.IgE-associatedfoodreactionssuchas S4 ANNALSOFALLERGY,ASTHMA&IMMUNOLOGY thosetriggeringatopicdermatitisaremoredifficulttodiscern reactiontothesuspectedfood;(2)patientswhohavemedical by history alone and may occur hours after food ingestion. conditions (eg, extensive atopic dermatitis or dermatogra- Itisimportanttorecognizethatthereareanumberofother phism that could interfere with interpretation of skin test immunologic and nonimmunologic reactions that can pro- results);(3)patientswithanonreactivehistaminecontrol(eg, ducesymptomsafterexposuretofoodsorfoodadditives(see due to medications that suppress skin test response); or (4) “Differential Diagnosis of Adverse Reactions to Foods” sec- women known to be pregnant (see Practice Parameters for tion). These reactions include conditions that are considered AllergyDiagnosticTesting).Ifthepatienthasahistoryofan to be examples of food intolerance and conditions that are anaphylactic reaction and test results for specific IgE anti- considered to be neither food allergy nor food intolerance, bodiesarepositive,nofurtherevaluationisusuallyrequired. suchasscombroidpoisoning.Specificclinicalandlaboratory Anumberofotherdiagnostictests(eg,atopypatchtests)are tests are available for many of these conditions. currently under investigation for IgE-mediated reactions to The evaluation of food allergy begins with a detailed foods. Provocation-neutralization is considered disproved as history,includingalistofsuspectfoods,thequantityoffood a diagnostic method in allergy, whereas hair analysis, food eliciting a reaction, the reproducibility of the reaction in specificIgGorimmunecomplexassays,andnewerversions relationshiptofoodingestion,thetimebetweenexposureand of the previously disproved cytotoxic tests are considered reaction, the clinical manifestations produced, whether there unproven or experimental. has been resolution of symptoms with elimination of the The rational selection, application, and interpretation of suspectfood,andtheoveralldurationofsymptomsandafter tests for food-specific IgE antibodies requires the following: eachexposure.Thiscanbeaugmentedbyawrittenrecording (1)considerationoftheepidemiologyandunderlyingimmu- of dietary intake. nopathophysiology of the disorder under investigation; (2) Aclinicallyrelevantphysicalexamination,withparticular the importance of making a definitive diagnosis; (3) estima- focus on suspected targeted organ systems (eg, cutaneous, tion of prior probability that a disorder or reaction is attrib- respiratory, and gastrointestinal) should be performed. The utable to a particular food; and (4) an understanding of the presence of atopic disorders such as asthma, atopic dermati- utility of the diagnostic tests being used. tis, and allergic rhinitis implies an increased risk of food Challenge with a suspected food may help to determine if allergy.Thephysicalexaminationmayalsorevealalternative thetestresultswereeitherfalselynegativeorfalselypositive. diagnoses that make food allergy less likely. Initial challenge can be performed in an open or single- Initial evaluation may be enhanced by certain testing pro- blinded fashion. When such challenges are performed, the cedures(see“DiagnosisofFoodAllergy”section).Skinprick physician must recognize the potential for bias that is intro- or puncture tests are often useful in screening patients with duced if both the patient and the physician are not blinded. suspectedfoodallergy.Commercialfoodextractsfromfoods Double-blind, placebo-controlled food challenge is most with stable proteins (eg, peanut, milk, egg, tree nuts, fish, likelytoprovidethephysicianwithavalidevaluationofthe shellfish)arereliabletodetectspecificIgEantibodiesinmost patient’scapacitytoreacttoagivenfoodandhasthehighest patients,whereasextractsfromfoodsthatcontainlabilepro- positive predictive value. In most patients, a diagnosis of an teins(eg,manyfruitsandvegetables)arelessreliable.Under IgE-mediated reaction to a particular food or food additive these conditions, pricking the food and then the patient may can be best made by obtaining a detailed history in conjunc- beuseful.Itisimportanttorecognizethatskinorinvitrotest tion with a positive test result for specific IgE antibodies to resultsmayremainpositiveeventhoughthepatient’sskinis the food and a positive challenge result with the food, espe- no longer clinically sensitive. Intracutaneous (intradermal) cially if the challenge is performed in a double-blind, place- skin tests are not recommended because they are potentially bo-controlled manner. Patients who have a history of reac- dangerous. In addition, they are overly sensitive and are tions to foods that could be IgE-mediated benefit from associated with an unacceptable rate of false-positive reac- consultation with an allergist-immunologist. tions. A positive skin test result may indicate food allergy Themanagementoffoodallergyreliesprimarilyonavoid- (positive predictive value (cid:1)50%), but a negative skin test anceofexposuretosuspectedorprovenfoods(see“General result virtually rules out an IgE-mediated mechanism (nega- Management of Food Allergy” section). This can best be tive predictive value (cid:2)95%). If done, skin testing should be doneifthespecificfoodsresponsibleforthepatient’ssymp- performedselectivelyforsuspectedfoods,becauseallergyto toms are identified by history and appropriate tests. If this is multiplefoodsisnotcommon.Fromanepidemiologicstand- not possible, patients with chronic symptoms may benefit point,generallylargerwheal-flarereactionsonprickorpunc- from an elimination diet, remembering that patients have an ture tests and higher concentrations of food-specific IgE increased risk of unintentional food allergen exposure in a measured by in vitro tests correlate with a greater likelihood numberofspecialcircumstances,suchasschoolsandrestau- of a reaction. rants (see “Management in Special Settings and Circum- In vitro tests may also provide useful information to eval- stances” section). Because of the potential for inadvertent uate possible IgE-mediated reactions. Situations in which exposure to foods, education of the patient and/or the pa- these tests may be particularly valuable include but are not tient’sadvocateisessential.Thisincludesreadinglabelsand limited to (1) patients with a history of a life-threatening recognition that unfamiliar terms may indicate the presence VOLUME 96, MARCH, 2006 S5 ofaclinicallyrelevantfood.Vagueorinaccuratelabelingand important for persistence of allergenicity beyond childhood cross-contamination of packaged foods or foods eaten in (eg, casein hypersensitivity). (B) restaurantsarepotentialhazards.Avoidanceoftheimplicated Summary Statement 8. The specific factor(s) that confer food may encourage future tolerance, especially with cow’s allergenicity rather than tolerogenicity are unknown. (E) milk,egg,andsoy.Patientoutcomesmaybeimprovedwhen Summary Statement 9. Characteristic IgE- and mast cell– avoidancemeasuresaremaintainedovertime.Thishasbeen mediatedmechanismsoccurinfood-inducedanaphylaxis,the showntobeassociatedwithlossofsymptomaticreactivityin oral allergy syndrome, and atopic dermatitis. (B) both children and adults to specific food allergens. Summary Statement 10. IgE-mediated reactions to foods Currently, there is no known oral or parenteral agent that may occur in neonates on first postnasal exposure, presum- has been shown consistently to prevent IgE-mediated reac- ably due to in utero sensitization. Since sensitization to di- tions to foods. Reliance on such treatment can lead to tragic etaryallergensinbreastmilkmayoccurinthelatepostnatal consequences. Immunotherapy to food proteins is currently period,breastfeedingmothers shouldavoidhighlyallergenic experimental. foods if familial allergic susceptibility is present. (B) Injectable epinephrine is the treatment of choice for an SummaryStatement11.Bothserumandsecretoryspecific anaphylactic reaction, regardless of the cause (see Anaphy- IgA to dietary proteins may be produced in healthy subjects laxis and Stinging Insect Hypersensitivity Practice Parame- and allergic patients. (B) ters). For this reason, patients who have experienced IgE- SummaryStatement12.ThesignificanceofIgM,IgG,and mediated reactions to a food or their caregivers should be IgGsubclassantibodies(eg,theroleofIgG4)infoodallergy educated and provided with injectable epinephrine to carry is less well understood and highly controversial. (B) withthem.Becauseanaphylacticreactionsmaybeprolonged SummaryStatement13.Theroleofcellularinvitrocorre- or biphasic, it is reasonable to instruct the patient to carry lates as diagnostic or prognostic indicators of food allergy is more than one epinephrine injector, to seek immediate med- not established. (B) ical care after a reaction, and to be monitored for an appro- Summary Statement 14. The role of specific cytokine pro- priate period (see “General Management of Food Allergy” filesinserumorperipheralmononuclearcellsoffoodallergic section). patients has not been established in the mechanism of food allergy. (B) SUMMARY STATEMENTS SummaryStatement15.Certainbacterialproducts,viruses, parasites,andT-cell–independentantigensstimulatesystemic Mucosal Immune Responses Induced By Foods immune responses rather than tolerance to the oral protein Summary Statement 1. Mucosal adaptive immunity has dual when coadministered with oral proteins. (B) functions of protection against enteric pathogens and main- Summary Statement 16. Sensitization to foods is much tenance of autotolerance against dietary proteins and com- more likely to occur in the early neonatal period. (B) mensal bacteria. (E) Summary Statement 17. Intestinal malabsorption and/or SummaryStatement2.Factorsthatregulategastrointestinal stasis may predispose patients to food allergy. (B) immune balance include the nature and dose of the antigen, Summary Statement 18. Genetic susceptibility, as defined immaturity of the host, genetic susceptibility, the rate of by single nucleotide polymorphisms or specific haplotypes, absorptionofadietaryprotein,andtheconditionsofantigen has been implicated in several common food allergy pheno- processing. (E) types. (B) SummaryStatement3.Foodallergensaregenerallyglyco- proteins with molecular weights ranging from 10 kDa to 70 The Clinical Spectrum of Food Allergy kDa. (E) Summary Statement 19. Allergic food reactions to foods SummaryStatement4.Themorecommonfoodallergensin (IgE-mediated reactions) are characterized by a temporal infantsandyoungchildrenarecow’smilk,hen’segg,peanut, relationshipbetweenthereactionandpriorexposuretofood. tree nuts, soybeans, and wheat, whereas the adult counter- Such reactions can be generalized or localized to a specific partsarepeanuts,treenuts,fish,crustaceans,mollusks,fruits, organ system and can be sudden, unexpected, severe, and and vegetables. (B) life-threatening. (D) SummaryStatement5.Majorallergenicepitopeshavebeen Summary Statement 20. Food allergens are a frequent identified and genes for some of the major allergens have cause of severe anaphylaxis, particularly in patients with been cloned and sequenced. (E) concomitant asthma and allergy to peanut, nut, or seafood. SummaryStatement6.Innateallergenicityoffoodsmaybe Such reactions may be biphasic or protracted. Food allergy determined by a combination of factors such as solubility, should be considered in the differential diagnosis of patients resistancetopH,heat,andproteolysisbydigestiveenzymes. who have idiopathic anaphylaxis. (C) (E) SummaryStatement21.Thepollen-foodallergysyndrome Summary Statement 7. Structural amino acid sequences, (oralallergysyndrome)ischaracterizedbytheacuteonsetof either sequential or conformational, account for cross-reac- oropharyngealpruritus,sometimesincludinglipangioedema, tivitybetweenfoods.Sequentialepitopesmaybeparticularly usually beginning within a few minutes after oral mucosal S6 ANNALSOFALLERGY,ASTHMA&IMMUNOLOGY contact with particular raw fruits and vegetables during eat- strategies for safeguarding against the development of food ing. (B) allergies has not been established. (B) Summary Statement 22. IgE-mediated gastrointestinal re- Cross-Reactivity of Food Allergens actions can present with only gastrointestinal symptoms or Summary Statement 33. Recent studies with molecular bio- with other nongastrointestinal manifestations. (D) logical techniques have characterized a variety of cross- Summary Statement 23. Allergic eosinophilic gastroenter- reacting allergens among foods. (C) itis(eosinophilicgastroenteropathy)ischaracterizedbypost- SummaryStatement34.Invitrocross-reactivitytomultiple prandial gastrointestinal symptoms associated with weight shared food allergens is common, but clinical correlation of loss in adults and failure to thrive in infants. (C) the cross-reactivity is variable. (C) Summary Statement 24. Upper and lower respiratory tract Summary Statement 35. Cow’s milk allergy is a common manifestations of IgE-mediated reactions to foods, such as disease of infancy and childhood. Goat’s milk cross-reacts rhinoconjunctivitis, laryngeal edema, and asthma, can occur with cow’s milk. Ninety percent of cow’s milk allergic pa- with or without other IgE-mediated symptoms. Isolated re- tients will react to goat and/or sheep’s milk. (A) spiratory manifestations from exposure to foods is rare and Summary Statement 36. Hen’s egg allergens cross-react hasbeenreportedmostfrequentlyinanoccupationalsetting. withcertainavianeggallergens,buttheclinicalimplications (C) of such cross-reactivity are unclear. (B) Summary Statement 25. Many inhaled food proteins in Summary Statement 37. In vitro cross-reactivity between occupationalsettingsmayaffectworkersregularlyexposedto soybean and other legume foods is extensive, but oral food such foods as flour (bakers’ asthma), egg white, and crusta- challenges demonstrate that clinical cross-reactivity to other ceans. (A) legumes in soy bean sensitive children is uncommon and SummaryStatement26.IgE-mediatedcutaneousreactions, generally transitory. (B) such as acute urticaria or angioedema and acute contact Summary Statement 38. Patients with peanut allergy gen- urticaria,areamongthemostcommonmanifestationsoffood erally tolerate other beans (95%), even soy. Evaluation of allergy. Food allergy is commonly suspected though rarely legume allergy in a patient with peanut allergy should be incriminated in chronic urticaria and angioedema but is im- individualized but avoidance of all legumes is generally un- plicated in at least one third of children with atopic derma- warranted. (B) titis. (B) Summary Statement 39.There is significant cross-reaction Prevalence and Epidemiology between different species of fish. Although there is limited Summary Statement 27. The prevalence of food allergy as investigation of the clinical relevance of such cross-reactiv- reported in double-blind studies is not as great as that per- ity, patients who are clinically allergic to any species of fish ceived by the public. It varies between 2% and 5% in most should be cautious about eating fish of another species until studies, with definite ethnic differences. (B) the clinical relevance of such cross-reactions to that species Summary Statement 28. The prevalence of food allergy is can be demonstrated by an accepted food challenge. (B) higher in certain subgroups such as individuals with atopic SummaryStatement40.Crustaceans,suchasshrimp,crab, dermatitis,certainpollensensitivities,orlatexsensitivity.(B) crawfish, and lobster, are a frequent cause of adverse food reactions, including life-threatening anaphylaxis. There is Natural History of Food Allergy considerable risk of cross-reactivity between crustaceans. Summary Statement 29. Although sensitivity to most food Less well defined is cross-reactivity between mollusks and allergenssuchasmilk,wheat,andeggstendstoremitinlate crustaceans. (C) childhood, persistence of certain food allergies such as pea- Summary Statement 41. Crustaceans do not cross-react nut,treenut,andseafoodmostcommonlycontinuesthrough- with vertebrate fish. (B) out one’s lifetime. (B) Summary Statement 42. Seafood allergy is not associated Summary Statement 30. The natural history of specific with increased risk of anaphylactoid reaction from radiocon- foods varies considerably. (C) trast media. (F) Risk Factors and Prevention of Food Allergy Summary Statement 43. Patients with wheat allergy alone Summary Statement 31. The rate of observed food allergy in showextensiveinvitrocross-reactivitytoothergrainsthatis children born to families with parental asthma was approxi- not reflected clinically. Therefore, elimination of all grains mately 4-fold higher than expected when compared with an from the diet (ie, wheat, rye, barley, oats, rice, corn) of a unselected population. (B) patient with grain allergy is clinically unwarranted and may SummaryStatement32.Foodallergypreventionstrategies be nutritionally detrimental. (B) include breastfeeding, maternal dietary restrictions during Summary Statement 44. Evaluation of cross-reactivity breastfeeding, delayed introduction of solid foods, delayed among tree nuts (walnut, hazelnut, Brazil nut, pecan) is introduction of particular allergenic foods, and the use of characterized by shared allergens among tree nuts and be- supplemental infant formulae that are hypoallergenic or of tween tree nuts and other plant-derived foods and pollen. reduced allergenicity. However, the effectiveness of these Clinical reactions to tree nuts can be severe and potentially VOLUME 96, MARCH, 2006 S7 fatal and can occur from the first exposure to a tree nut in beverage consumption occur some but not all the time, sug- patientsallergictoothertreenuts.Inmostcases,elimination gesting that the reaction occurs only when an additive is of all tree nuts from the diet is appropriate. (C) present. (C) Summary Statement 45. Since the proteins of cacao nut Summary Statement 56. Management entails avoiding undergo extensive modification into relatively nonallergenic foods or beverages that contain the implicated additive and complexes during the processing of commercial chocolate, using self-injectable epinephrine for life-threatening reac- clinical sensitivity to chocolate is vanishingly rare. (D) tions,especiallyforindividualswhoaresulfitesensitive.(B) Summary Statement 46. Although IgE-mediated reactions Genetically Modified Foods to fruits and vegetables are commonly reported, clinically relevant cross-reactivity resulting in severe reactions is un- SummaryStatement57.Manyofthemajorfoodgroupshave common. (C) undergone modification by gene manipulation or replace- Summary Statement 47. The latex-fruit syndrome is the ment, and several of these food products are currently on result of cross-reactivity between natural rubber latex pro- grocery store shelves. (C) teins and fruit proteins. Class 1 chitinases (Hev b 6, hevein- Summary Statement 58. The possibility exists that trans- like proteins), profilins (Hev b 8), (cid:3)-1, 3-gluconases (Hev b genicplantproteinsinnovelgeneticallymodifiedfoodscould 2), and other cross-reactive polypeptides have been impli- cause severe food allergy, including anaphylactic shock, if cated. The most commonly reported cross-reactive foods allergenic determinants (amino acid sequences) in the trans- includebanana,avocado,kiwi,andchestnut,butmanyother genic proteins share a high degree of homology to those of fruits and some nuts have been identified in cross-reactivity known food allergens. (E) studies. (D) Summary Statement 59. As illustrated by recent introduc- SummaryStatement48.Seedstorageproteinsappeartobe tion of corn engineered to contain a pesticide, (cid:4)endotoxin the main allergens in the edible seeds; in particular, 2S (derived from Bacillus thuringiensis), into the human food albumin family proteins (part of the cereal prolamin super- chain, food allergy to such engineered foods could occur in family)havebeendemonstratedasallergensinsesame,mus- workers previously exposed and sensitized to this endotoxin tard,sunflower,andcottonseed.Cross-reactivityhasnotbeen or in other highly susceptible atopic patients. (A) well-studied. (E) Summary Statement 60. The potential allergenicity of Adverse Reactions to Food Additives newlydevelopedgeneticallymodifiedfoodsshouldbeinves- SummaryStatement49.Thenumberofadditivesusedbythe tigated on a case-by-case basis by individual commercial foodindustryisextensive.Onlyasmallnumberofadditives developers and appropriate regulatory agencies. (D) havebeenimplicatedinIgE-mediatedorother(immunologic Diagnosis of Food Allergy or nonimmunologic) adverse reactions. Adverse reactions to Summary Statement 61. The primary tools available to diag- food additives, therefore, are rare. (C) noseadversereactionstofoodsincludehistory(includingdiet SummaryStatement50.Foodadditivesmaycauseanaphy- records), physical examination, skin prick or puncture tests, laxis,urticariaorangioedema,orasthma.Thesereactionscan serumtestsforfoodspecificIgEantibodies,trialelimination be severe or even life-threatening; fatalities have been de- diets, and oral food challenges. (B) scribed. (C) SummaryStatement62.Adetaileddietaryhistory,attimes Summary Statement 51. Tartrazine (FD&C yellow No. 5) augmented with written diet records, is necessary to deter- sensitivityisextremelyrare.Thereisnoconvincingevidence minethelikelihoodthatfoodiscausingthedisorder,identify to support the contention that tartrazine “cross-reacts” with the potential triggers, and determine the potential immuno- cyclooxygenase-inhibiting drugs. (B) pathophysiology. (D) Summary Statement 52. Monosodium glutamate (MSG) Summary Statement 63. A physical examination may re- sensitivityisararecauseofurticariaorangioedema.(C)Itis veal the presence of atopic disorders, such as asthma, atopic also a rare cause of bronchospasm in patients with asthma. dermatitis,andallergicrhinitis,thatindicateanincreasedrisk (B) SummaryStatement53.Sulfites producebronchospasmin for food allergy or reveal alternative diagnoses that may 5% of the asthmatic population, in most cases due to gener- reduce the likelihood of food allergy. (C) ationofsulfurdioxideintheoropharynx.(A)Sulfite-induced Summary Statement 64. Tests for food specific IgE anti- anaphylaxis has also been described. (B) body include PSTs (prick or puncture) and serum assays. SummaryStatement54.“Natural”foodadditives,including These tests are highly sensitive (generally (cid:1)90%) but only annatto, carmine, and saffron, as well as erythritol (ERT; modestlyspecific(approximately50%)andthereforearewell 1,2,3,4-butanetetrol), a sweetener, may be rare causes of suitedforusewhensuspicionofaparticularfoodorfoodsis anaphylaxis. (C) high but are poor for the purpose of screening (eg, using Summary Statement 55. Adverse reactions (anaphylaxis, panels of tests without consideration of likely causes). (B) urticaria or angioedema, or bronchospasm) from food addi- Summary Statement 65. Intracutaneous (intradermal) skin tives should be suspected when symptoms after food or tests for foods are potentially dangerous, overly sensitive S8 ANNALSOFALLERGY,ASTHMA&IMMUNOLOGY (increasing the rate of a false-positive test result), and not sumption, carrying self-injectable epinephrine, exercising recommended. (D) with a “buddy,” and wearing medic-alert jewelry. (C) Summary Statement 66. Results of PSTs and serum tests Differential Diagnosis of Adverse Reactions to Foods for food specific IgE antibody may be influenced by patient Summary Statement 77. Non–IgE-mediated immunologic re- characteristics (eg, age), the quality and characteristics of actions to foods have been implicated in such entities as (1) reagents(eg,variationsincommercialextracts,cross-reacting food-inducedenterocolitisandcolitis,(2)malabsorptionsyn- proteins among food extracts), and techniques (eg, assay dromes (eg, celiac disease), (3) cow’s milk–induced syn- types, skin test devices, location of test placement, mode of dromes, and (4) dermatitis herpetiformis. (C) measurement). (B) Summary Statement 78. Food-induced enterocolitis and SummaryStatement67.Increasinglyhigherconcentrations colitisaremostcommonlyseenininfantsseveralhoursafter of food specific IgE antibodies (reflected by increasingly ingestion of food proteins, most notably those in cow’s milk larger PST response size and/or higher concentrations of or soy formulas. Infants with food-induced enterocolitis de- food-specific serum IgE antibody) correlate with an increas- velopsevereprotractedvomitinganddiarrheacomparedwith ing risk for a clinical reaction. (C) infantswithfood-inducedcolitiswhousuallyappearhealthy. Summary Statement 68. A trial elimination diet may be Bothgroupsofpatientspresentwithbloodandeosinophilsin helpful to determine if a disorder with frequent or chronic the stool, although colitis more often presents with gross symptoms is responsive to dietary manipulation. (D) blood. (C) Summary Statement 69. Graded oral food challenge is a Summary Statement 79. Immune-mediated malabsorption useful means to diagnose an adverse reaction to food. (B) syndromes that result in diarrhea and weight loss (or lack of SummaryStatement70.Anumberofadditionaldiagnostic weightgain)mayoccursecondarytointolerancetoavariety tests are under investigation, including atopy patch tests, of food proteins, including those in cow’s milk, soy, wheat, basophil activation assays, and tests for IgE binding to spe- other cereal grains, and eggs. (C) cific epitopes. (E) Summary Statement 80. Celiac disease is a severe form of SummaryStatement71.Sometests,includingprovocation malabsorption characterized by total villous atrophy and ex- neutralization, cytotoxic tests, IgG antibodies directed to tensive cellular infiltrates due to an immunologic reaction to foods, and hair analysis, are either disproved or unproven; gliadin, a component of gluten found in wheat, oat, rye, and therefore,theyarenotrecommendedforthediagnosisoffood barley. The diagnosis of the disease is crucial, since the allergy. (C) removal of gluten from the diet can lead to reversal of Summary Statement 72. Ancillary tests may be needed to histopathologic changes and recovery of gastrointestinal confirm the diagnosis of food intolerance or immune reac- function. (C) tions to foods, such as breath hydrogen tests for lactose Summary Statement 81. In a subset of infants, colic and intolerance or gastrointestinal biopsy to determine eosino- gastroesophageal reflux disease have been attributed to ad- philic inflammation or atrophic villi. (D) verse reactions to cow’s milk. However, an immunologic SummaryStatement73.Therationalselection,application, basis for these conditions has not been clearly established. and interpretation of tests for food-specific IgE antibodies (A) require consideration of the epidemiology and underlying Summary Statement 82. Dermatitis herpetiformis is char- immunopathophysiology of the disorder under investigation, acterized by a chronic, intensely pruritic, papulovesicular the importance of making a definitive diagnosis, estimation rash symmetrically distributed over the extensor surfaces of of prior probability that a disorder or reaction is attributable theextremitiesandthebuttocksassociatedwithgluteninges- to particular foods, and an understanding of the test utility. tion and often with gluten-sensitive enteropathy. Direct im- (D) munofluorescence or specific immunologic assays may be helpful in making the diagnosis. (B) Food-Dependent Exercise-Induced Anaphylaxis (EIA) Summary Statement 83. Cow’s milk–induced pulmonary SummaryStatement74.Individualswithfood-dependentEIA hemosiderosis (Heiner syndrome) is an extremely rare con- develop neither anaphylaxis with ingestion of food without dition in infants and toddlers that also may be related to egg subsequent exercise nor anaphylaxis after exercise without orporkhypersensitivityandforwhichtheimmunopathology temporally related ingestion of food. (A) is poorly understood. It is characterized clinically by recur- SummaryStatement75.Twosubsetsofpatientswithfood- rent episodes of pneumonia associated with pulmonary infil- dependentEIAhavebeendescribed1:onesubsetmaydevelop trates, hemosiderosis, gastrointestinal blood loss, iron-defi- anaphylaxiswhenexercisingintemporalproximitytoinges- ciency anemia, and failure to thrive. The presence of tion of any type of food2; another subset may experience precipitating antibodies to the responsible antigen is neces- anaphylaxis with exercise in conjunction with ingestion of a sary but not sufficient to make the diagnosis. (C) specific food. (A) Summary Statement 84. Toxic food reactions, bacterial Summary Statement 76. Management of food-dependent contamination of food, and pharmacologic food reactions EIA entails avoiding exercising in proximity to food con- maymimicIgE-mediatedreactionsandshouldbeconsidered VOLUME 96, MARCH, 2006 S9 early in the differential diagnosis because of the serious SummaryStatement94.Ifthereisahistoryofsuspected nature of such reactions. (C) or proven IgE-mediated systemic reactions to foods, in- SummaryStatement85.Pharmacologicadversefoodreac- jectable epinephrine should be given to patients and/or tions occur after ingestion of foods with pharmacologically caregiverstocarrywiththemandtheyshouldbeinstructed active substances, such as vasoactive amines, in particular in its use. (F) histamine (scombroid poisoning), and produce a wide range Summary Statement 95. Prophylactic medications have ofclinicalmanifestations,especiallygastrointestinalandcen- not been shown to be effective in consistently preventing tral nervous system in nature. Patients may present with severe, life-threatening reactions to foods and may mask a flushing,sweating,nausea,vomiting,diarrhea,headache,pal- less severe IgE-mediated reaction to a food, knowledge of pitations, dizziness, swelling of the face and tongue, respira- which could prevent a more severe reaction to that food in tory distress, and shock. (C) the future. (D) Summary Statement 86. Enzymatic food reactions are causedbytheingestionofnormaldietaryamountsoffoodsin Management in Special Settings and Circumstances individuals susceptible to such reactions because of medica- Summary Statement 96. Fatal and near-fatal food anaphylac- tions, disease states, malnutrition, or inborn errors of metab- ticreactionstendtooccurawayfromhomeafteranuninten- olism (eg, lactose intolerance). (C) tional ingestion of a food allergen by individuals with a Summary Statement 87. Reactions not related to specific known allergy to the same food. (C) food ingestion but due to the act of eating that can be Summary Statement 97. Delay in the administration of misdiagnosed as reactions to foods include gustatory or va- injectable epinephrine is a common feature of fatal food somotorrhinitis,carcinoidsyndrome,idiopathicanaphylaxis, allergic reactions. (C) systemic mastocytosis, inflammatory bowel disease, and ir- Summary Statement 98. Peanut and tree nuts account for ritable bowel syndrome. (C) mostfatalandnear-fatalfoodallergicreactionsintheUnited Summary Statement 88. Conditions incorrectly identified States. (C) as being related to food ingestion include multiple sclerosis, SummaryStatement99.Allergicreactionsthatresultfrom attention-deficitdisorder,autismandotherbehavioralcondi- direct skin contact with food allergens are generally less tions, chronic fatigue syndrome, and the “yeast connection.” severethanreactionsduetoallergeningestion.Reactionsthat (C) result from inhalation of food allergens are generally less General Management of Food Allergy frequentandlessseverethanreactionscausedbyeitherdirect Summary Statement 89. The key to the management of pa- skincontactoringestion.Exceptionstothesegeneralizations tientswithfoodallergyisavoidanceoffoodsknowntohave are more likely in occupational environments and other set- or suspected of having caused a reaction. (F) tingsinwhichfoodallergensensitizationoccurredviaeither SummaryStatement90.Sinceeliminationdietsmayleadto inhalation or skin contact. (B) malnutrition or other serious adverse effects (eg, personality Summary Statement 100. Schools and childcare centers change), every effort should be made to ensure that the shouldhavepoliciesforfacilitatingfoodallergenavoidance, dietaryneedsofthepatientaremetandthatthepatientand/or including staff education regarding label reading and cross- caregiver(s) are fully educated in dietary management. Once contamination, prohibition of food or utensil sharing, and thediagnosisoffoodallergyisconfirmed,thepatientshould increased staff supervision during student meals. (D) be advised to avoid eating the food. (D) Summary Statement 101. Schools and childcare centers Summary Statement 91. In some cases, severe allergic should have policies ensuring prompt treatment of food ana- reactionsmaybeseeninpatientswhoonlyinhaleorcomein phylaxis, including a requirement for physician-prescribed contact with food allergens, thereby making avoidance even treatmentprotocolsforfoodallergicstudents,staffeducation more difficult. (D) regarding recognition and treatment of anaphylaxis, and the Summary Statement 92. The successful avoidance of food ready availability of injectable epinephrine. (D) allergens relies on (1) identification in each patient of the SummaryStatement102.Itisimportanttoinformworkers specific food that caused the reaction; (2) recognition of inarestaurantorotherfoodestablishmentaboutahistoryof cross-reacting allergens in other foods; (3) education of the a systemic food allergic reaction, although this does not patientand/orcaregiveraboutavoidancemeasures,withpar- ensure that the meal will be free of the offending food. (C) ticular emphasis on hidden food allergens or additives; and Summary Statement 103. Allograft transplant recipients (4) willingness of the educated patient and/or caregiver to may acquire specific food allergic sensitivities from organ read labels carefully, inquire at restaurants, and take other measures to prevent inadvertent exposure to known or sus- donors. (B) pected allergens. (D) Summary Statement 104. Patients with latex allergy have Summary Statement 93. In selected cases, reevaluation of anincreasedriskofexperiencingIgE-mediatedfood-induced patients with food allergy may be important to determine if symptoms, including anaphylaxis, particularly when ingest- food allergy has been lost over time. (F) ing banana, avocado, kiwi, or chestnut. (C) S10 ANNALSOFALLERGY,ASTHMA&IMMUNOLOGY

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Autotolerance refers to the state of balance of the innate and adaptive . Adverse reactions to foods have been reported in up to 25% of the population at some
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