Portal de Periódicos da CAPES

ICON: Food allergy

2012; Elsevier BV; Volume: 129; Issue: 4 Linguagem: Inglês

10.1016/j.jaci.2012.02.001

1097-6825

A. Wesley Burks, Mimi L.K. Tang, Scott H. Sicherer, Antonella Muraro, Philippe Eigenmann, Motohiro Ebisawa, Alessandro Fiocchi, Wen Chin Chiang, Kirsten Beyer, Robert A. Wood, Jonathan O’B Hourihane, Stacie M. Jones, Gideon Lack, Hugh A. Sampson,

Asthma and respiratory diseases

Food allergies can result in life-threatening reactions and diminish quality of life. In the last several decades, the prevalence of food allergies has increased in several regions throughout the world. Although more than 170 foods have been identified as being potentially allergenic, a minority of these foods cause the majority of reactions, and common food allergens vary between geographic regions. Treatment of food allergy involves strict avoidance of the trigger food. Medications manage symptoms of disease, but currently, there is no cure for food allergy. In light of the increasing burden of allergic diseases, the American Academy of Allergy, Asthma & Immunology; European Academy of Allergy and Clinical Immunology; World Allergy Organization; and American College of Allergy, Asthma & Immunology have come together to increase the communication of information about allergies and asthma at a global level. Within the framework of this collaboration, termed the International Collaboration in Asthma, Allergy and Immunology, a series of consensus documents called International Consensus ON (ICON) are being developed to serve as an important resource and support physicians in managing different allergic diseases. An author group was formed to describe the natural history, prevalence, diagnosis, and treatment of food allergies in the context of the global community. Food allergies can result in life-threatening reactions and diminish quality of life. In the last several decades, the prevalence of food allergies has increased in several regions throughout the world. Although more than 170 foods have been identified as being potentially allergenic, a minority of these foods cause the majority of reactions, and common food allergens vary between geographic regions. Treatment of food allergy involves strict avoidance of the trigger food. Medications manage symptoms of disease, but currently, there is no cure for food allergy. In light of the increasing burden of allergic diseases, the American Academy of Allergy, Asthma & Immunology; European Academy of Allergy and Clinical Immunology; World Allergy Organization; and American College of Allergy, Asthma & Immunology have come together to increase the communication of information about allergies and asthma at a global level. Within the framework of this collaboration, termed the International Collaboration in Asthma, Allergy and Immunology, a series of consensus documents called International Consensus ON (ICON) are being developed to serve as an important resource and support physicians in managing different allergic diseases. An author group was formed to describe the natural history, prevalence, diagnosis, and treatment of food allergies in the context of the global community. The International Collaboration in Asthma and Allergy initiated an international coalition among the American Academy of Allergy, Asthma & Immunology; European Academy of Allergy and Clinical Immunology; World Allergy Organization; and American College of Allergy, Asthma and Immunology on food allergy. An author group was formed and then divided into individual committees. Within the committee, teams of authors were created to generate content for specific sections of the article. Content was derived from literature searches, relevant published guidelines, and clinical experience. After a draft of the document was assembled, it was collectively reviewed and revised by the authors. Where evidence was lacking or conflicting, the information presented represents the consensus expert opinion of the group.Definition of the disease and epidemiologic featuresFood allergyThe term food allergy refers to an immune response directed toward food.1Chafen J.J.S. Newberry S.J. Riedl M.A. Bravata D.M. Maglione M. Suttorp M.J. et al.Diagnosing and managing common food allergies: a systematic review.JAMA. 2010; 303: 1848-1856Crossref PubMed Scopus (371) Google Scholar As defined in the 2010 US National Institutes of Allergy and Infectious Diseases (NIAID)–sponsored guidelines, food allergy is an “adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food.”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: S1-S58PubMed Google Scholar This definition encompasses immune responses that are IgE mediated, non–IgE mediated, or a combination of both and is in agreement with other international guidelines.3Sackeyfio A. Senthinathan A. Kandaswamy P. Barry P.W. Shaw B. Baker M. Diagnosis and assessment of food allergy in children and young people: summary of NICE guidance.BMJ. 2011; 342: d747Crossref PubMed Scopus (31) Google Scholar, 4Fiocchi A. Schünemann H.J. Brozek J. Restani P. Beyer K. Troncone R. et al.Diagnosis and Rationale for Action Against Cow’s Milk Allergy (DRACMA): a summary report.J Allergy Clin Immunol. 2010; 126 (e12): 1119-1128Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar, 5Urisu A. Ebisawa M. Mukoyama T. Morikawa A. Kondo N. Japanese guideline for food allergy.Allergol Int. 2011; 60: 221-236Crossref PubMed Scopus (47) Google ScholarIgE-mediated reactions are characterized by an acute onset of symptoms generally within 2 hours after ingestion of or exposure to the trigger food. IgE-mediated reactions to foods typically involve the skin, gastrointestinal tract, and respiratory tract. Allergic sensitization occurs when food-specific IgE (sIgE) antibodies are produced by plasma cells that have differentiated from allergen-specific B lymphocytes. The sIgE antibodies bind to the surface of tissue mast cells and blood basophils, and on re-exposure to the food, antigenic proteins in the food bind to and cross-link these cell surface–bound sIgE antibodies, which triggers the release of symptom-causing mediators, such as histamine and leukotrienes. Subjects can have allergic sensitization (production of sIgE) to food allergens without having clinical symptoms of an allergic reaction on exposure. Thus sensitization alone is not sufficient to define food allergy. An sIgE-mediated food allergy requires both the presence of sensitization and the development of specific signs and symptoms on exposure to that food.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: S1-S58PubMed Google ScholarNon–IgE-mediated immunologic reactions (eg, cell mediated) include food protein–induced enterocolitis, proctocolitis, and enteropathy syndromes. These conditions primarily affect infants or young children who present with abdominal complaints, such as vomiting, abdominal cramps, diarrhea, and occasionally blood in the stool and failure to thrive or poor weight gain. Examples of food allergy comorbidities with mixed IgE- and non–IgE-mediated causes include eosinophilic esophagitis and atopic dermatitis.Table I shows specific food-induced allergic conditions on the basis of pathophysiology. The table does not include symptoms or disorders that are not specific clinical syndromes associated with food allergy; thus infantile colic, constipation, and gastrointestinal reflux disease are not listed. Isolated chronic rhinitis and asthma are not commonly attributed to food allergy; however, occupational exposure can trigger asthma (eg, Baker's asthma from wheat) or contact dermatitis. Celiac disease (and dermatitis herpetiformis associated with celiac disease) is a cell-mediated response against an enzyme, tissue transglutaminase, that can be triggered by an immune response to a food protein, gluten. Because celiac disease is an autoimmune disorder with distinct symptoms and prognosis different than those of atopic disorders, it will not be discussed further in this document. There are numerous adverse responses to foods that do not involve an immune response and therefore are not considered the result of food allergies.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: S1-S58PubMed Google Scholar These include metabolic disorders, such as lactose and alcohol intolerance, responses to pharmacologically active food components (eg, caffeine), or illness in response to toxins from microbial contamination.6Sicherer S.H. Sampson H.A. Food allergy.J Allergy Clin Immunol. 2010; 125: S116-S125Abstract Full Text Full Text PDF PubMed Scopus (862) Google Scholar Certain psychological or neurological responses, such as food aversion or rhinorrhea caused by spicy foods, can also mimic food allergy but are not considered allergic disorders.Table ISpecific food-induced allergic conditionsPathologyDisorderKey featuresMost common causal foodsIgE mediated (acute onset)Acute urticaria/angioedemaFood commonly causes acute (20%) but rarely chronic urticaria.Primarily “major allergens” (see text)Contact urticariaDirect skin contact results in lesions. Rarely this is due to direct histamine release (nonimmunologic).MultipleAnaphylaxisRapidly progressive, multiple organ system reaction can include cardiovascular collapse.Any but more commonly peanut, tree nuts, shellfish, fish, milk, and eggFood-associated, exercise-induced anaphylaxisFood triggers anaphylaxis only if ingestion is followed temporally by exercise.Wheat, shellfish, and celery most often describedOral allergy syndrome (pollen-associated food allergy syndrome)Pruritus and mild edema are confined to oral cavity and uncommonly progress beyond the mouth (∼7%) and rarely to anaphylaxis (1% to 2%). Might increase after pollen season.Raw fruit/vegetables; cooked forms tolerated; examples of relationships: birch (apple, peach, pear, carrot), ragweed (melons)Immediate gastrointestinal hypersensitivityImmediate vomiting, painMajor allergensCombined IgE and cell mediated (delayed onset/chronic)Atopic dermatitisAssociated with food allergy in ∼35% of children with moderate-to-severe rashMajor allergens, particularly egg, milkEosinophilic esophagitisSymptoms might include feeding disorders, reflux symptoms, vomiting, dysphagia, and food impaction.MultipleEosinophilic gastroenteritisVary on site(s)/degree of eosinophilic inflammation; might include ascites, weight loss, edema, obstructionMultipleCell mediated (delayed onset/chronic)Food protein–induced enterocolitis syndromePrimarily affects infants; chronic exposure: emesis, diarrhea, poor growth, lethargy; re-exposure after restriction: emesis, diarrhea, hypotension (15%) 2 hours after ingestionCow’s milk, soy, rice, oat, meatFood protein–induced allergic proctocolitisMucus-laden, bloody stools in infantsMilk (through breast-feeding)Allergic contact dermatitisOften occupational because of chemical moieties, oleoresins. Systemic contact dermatitis is a rare variant because of ingestionSpices, fruits, vegetablesHeiner syndromePulmonary infiltrates, failure to thrive, iron deficiency anemiaCow’s milk Open table in a new tab Food allergensFood allergens, which are usually proteins but sometimes haptens, are recognized by allergen-specific immune cells and elicit specific immunologic reactions.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: S1-S58PubMed Google Scholar Most food allergens can cause reactions when ingested either in the raw form or after being cooked or even digested, but some allergens, such as those in fruits and vegetables, cause allergic reactions primarily if eaten raw. Food allergens can also cause reactions if the allergenic proteins are inhaled, although this should be differentiated from simply inhaling the fragrance of a food, which does not cause allergic reactions. Cross-reactivity can occur when a food allergen has structural or sequence similarity with a different food allergen or aeroallergen. The likelihood of having clinical allergic reactions to cross-reactive allergens is highly variable and depends on the type of food. For example, clinical cross-reactivity among legumes is generally uncommon (eg, most persons with peanut allergy tolerate beans and peas), whereas clinical cross-reactivity among different types of crustacean shellfish is common.Although any food can trigger an allergic response and more than 170 foods have been reported to cause IgE-mediated reactions, a minority of foods cause the majority of allergic reactions, with most being attributed to the “major food allergens” peanut, tree nuts, egg, milk, fish, crustacean shellfish, wheat, and soy.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: S1-S58PubMed Google Scholar Celery, mustard, sesame, lupine, and molluscan shellfish have been identified as significant allergens in European countries, and in Japan buckwheat is also a common allergen.7Akiyama H. Imai T. Ebisawa M. Japan food allergen labeling regulation-history and evaluation.Adv Food Nutr Res. 2011; 62: 139-171Crossref PubMed Scopus (113) Google ScholarProtein-containing food additives and coloring agents, such as annatto, carmine, and gelatin, can induce allergic reactions. Chemical additives, such as artificial flavors (eg, tartrazine) and preservatives (eg, glutamates and sulfites), might cause adverse reactions, but an immune mechanism has not been identified, and such reactions are classified as intolerances.Symptoms and severityThe likelihood of an allergic reaction is related to the level of sIgE. Symptoms of food allergy (Table II)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: S1-S58PubMed Google Scholar can occur within minutes to hours of ingesting the trigger food and can vary in severity from mild to life-threatening. Severity of allergic reactions varies based on the amount of food ingested, coingestion of other foods, and preparation of the food (cooked, raw, or processed).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: S1-S58PubMed Google Scholar Severity also can be influenced by the patient’s age, as well as rapidity of absorption, which can be influenced by whether the food was eaten on an empty stomach or close to a time of exercise. The presence of other comorbid conditions, such as asthma or atopic dermatitis, also can influence severity. The severity of a reaction cannot be accurately predicted by the severity of past reactions or by the sIgE levels or size of a skin prick test (SPT) wheal. Although reactions after a severe reaction are also likely to be severe,8Vander Leek T.K. Liu A.H. Stefanski K. Blacker B. Bock S.A. The natural history of peanut allergy in young children and its association with serum peanut-specific IgE.J Pediatr. 2000; 137: 749-755Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar mild reactions can also be followed by more severe reactions.9Ewan P.W. Clark A.T. Long-term prospective observational study of patients with peanut and nut allergy after participation in a management plan.Lancet. 2001; 357: 111-115Abstract Full Text Full Text PDF PubMed Scopus (163) Google ScholarTable IISymptoms of food-induced allergic reactionsOriginally printed in Boyce et al.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: S1-S58PubMed Google Scholar Reproduced with permission from Elsevier Limited.Target organImmediate symptomsDelayed symptomsCutaneousErythemaErythemaPruritusFlushingUrticariaPruritusMorbilliform eruptionMorbilliform eruptionAngioedemaAngioedemaEczematous rashOcularPruritusPruritusConjunctival erythemaConjunctival erythemaTearingTearingPeriorbital edemaPeriorbital edemaUpper respiratoryNasal congestionPruritusRhinorrheaSneezingLaryngeal edemaHoarsenessDry staccato coughLower respiratoryCoughCough, dyspnea, and wheezingChest tightnessDyspneaWheezingIntercostal retractionsAccessory muscle useGastrointestinal (oral)Angioedema of lips, tongue, or palateOral pruritusTongue swellingGastrointestinal (lower)NauseaNauseaColicky abdominal painAbdominal painRefluxRefluxVomitingVomitingDiarrheaDiarrheaHematocheziaIrritability and food refusal with weight loss (young children)CardiovascularTachycardia (occasionally bradycardia in anaphylaxis)HypotensionDizzinessFaintingLoss of consciousnessMiscellaneousUterine contractionsSense of “impending doom” Open table in a new tab Food-induced anaphylaxis is a serious allergic reaction that is rapid in onset and can cause death.10Sampson H.A. Muñoz-Furlong A. Bock S.A. Schmitt C. Bass R. Chowdhury B.A. et al.Symposium on the definition and management of anaphylaxis: summary report.J Allergy Clin Immunol. 2005; 115: 584-591Abstract Full Text Full Text PDF PubMed Scopus (379) Google Scholar IgE-mediated food-induced anaphylaxis involves systemic mediator release from sensitized mast cells and basophils. In patients with food-dependent, exercise-induced anaphylaxis, whether a reaction occurs depends on the amount of time between food consumption and exercise, usually within 2 hours.Fatalities are primarily from allergic reactions to peanuts and tree nuts, are associated with delayed treatment with epinephrine (adrenaline), and occur more often in teenagers and young adults with asthma and a previously diagnosed food allergy.11Pumphrey R.S.H. Gowland M.H. Further fatal allergic reactions to food in the United Kingdom, 1999-2006.J Allergy Clin Immunol. 2007; 119: 1018-1019Abstract Full Text Full Text PDF PubMed Scopus (431) Google Scholar, 12Bock S.A. Muñoz-Furlong A. Sampson H.A. Fatalities due to anaphylactic reactions to foods.J Allergy Clin Immunol. 2001; 107: 191-193Abstract Full Text PDF PubMed Scopus (1360) Google Scholar, 13Liew W.K. Williamson E. Tang M.L.K. Anaphylaxis fatalities and admissions in Australia.J Allergy Clin Immunol. 2009; 123: 434-442Abstract Full Text Full Text PDF PubMed Scopus (373) Google Scholar Other factors related to having fatal or near-fatal reactions include association of food allergy with asthma, absence of skin symptoms, patient denial of symptoms, concomitant intake of alcohol, or reliance on oral antihistamines to manage symptoms.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: S1-S58PubMed Google Scholar, 11Pumphrey R.S.H. Gowland M.H. Further fatal allergic reactions to food in the United Kingdom, 1999-2006.J Allergy Clin Immunol. 2007; 119: 1018-1019Abstract Full Text Full Text PDF PubMed Scopus (431) Google Scholar, 13Liew W.K. Williamson E. Tang M.L.K. Anaphylaxis fatalities and admissions in Australia.J Allergy Clin Immunol. 2009; 123: 434-442Abstract Full Text Full Text PDF PubMed Scopus (373) Google ScholarNatural history and development of toleranceThe timing of food allergy development and resolution is variable and appears to be influenced by several factors. Food allergy in adults can represent a persistent allergy from childhood or de novo sensitization. There are few data regarding food allergy beginning in adulthood, but empiric evidence suggests food allergy that starts in adulthood often persists. In contrast, food allergies that start in childhood are often outgrown. The proportions of children who will outgrow allergy to a given food vary between analyses, but allergy to milk, egg, soy, or wheat is more likely to be outgrown than allergy to tree nuts or peanut.14Høst A. Halken S. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction.Allergy. 1990; 45: 587-596Crossref PubMed Scopus (620) Google Scholar, 15Sicherer S.H. Clinical aspects of gastrointestinal food allergy in childhood.Pediatrics. 2003; 111: 1609-1616PubMed Google Scholar Resolution of a food allergy can occur as late as the teenage years. Allergy to fish or crustacean shellfish, which most commonly develops in adulthood, usually persists.16Rona R.J. Keil T. Summers C. Gislason D. Zuidmeer L. Sodergren E. et al.The prevalence of food allergy: a meta-analysis.J Allergy Clin Immunol. 2007; 120: 638-646Abstract Full Text Full Text PDF PubMed Scopus (1040) Google Scholar, 17Sicherer S.H. Muñoz-Furlong A. Sampson H.A. Prevalence of seafood allergy in the United States determined by a random telephone survey.J Allergy Clin Immunol. 2004; 114: 159-165Abstract Full Text Full Text PDF PubMed Scopus (447) Google ScholarIn studies that examine the development of tolerance, case definitions of “food allergy” and “tolerance” are variable and strongly influence outcomes.18Wood R.A. The natural history of food allergy.Pediatrics. 2003; 111: 1631-1637PubMed Google Scholar Some studies only report rates of sensitization, whereas other studies focus on clinical reactivity to specific foods. The definition of clinical reactivity is also not consistent between studies in that some rely solely on parental reports of food reactions, whereas others use food challenges or other more objective measures of true food allergy. These details are important in that a history of an adverse food reaction or even evidence of sensitization does not necessarily mean that a patient will exhibit a clinical reaction on exposure to that food.For the purposes of this review, a search of the PubMed database with the key words “food allergy” and “natural history” from 2003 to 2011 was conducted. Also reviewed were articles cited in relevant articles. Two reviewers independently evaluated each article’s pertinence. Reviewed articles are summarized in Table III.19Pyziak K. Kamer B. Natural history of IgE-dependent food allergy diagnosed in children during the first three years of life.Adv Med Sci. 2011; 56: 48-55Crossref PubMed Scopus (15) Google Scholar, 20Shek L.P.C. Soderstrom L. Ahlstedt S. Beyer K. Sampson H.A. Determination of food specific IgE levels over time can predict the development of tolerance in cow’s milk and hen’s egg allergy.J Allergy Clin Immunol. 2004; 114: 387-391Abstract Full Text Full Text PDF PubMed Scopus (249) Google Scholar, 21Skripak J.M. Matsui E.C. Mudd K. Wood R.A. The natural history of IgE-mediated cow’s milk allergy.J Allergy Clin Immunol. 2007; 120: 1172-1177Abstract Full Text Full Text PDF PubMed Scopus (592) Google Scholar, 22Savage J.H. Kaeding A.J. Matsui E.C. Wood R.A. The natural history of soy allergy.J Allergy Clin Immunol. 2010; 125: 683-686Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar, 23Keet C.A. Matsui E.C. Dhillon G. Lenehan P. Paterakis M. Wood R.A. The natural history of wheat allergy.Ann Allergy Asthma Immunol. 2009; 102: 410-415Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar, 24Savage J.H. Matsui E.C. Skripak J.M. Wood R.A. The natural history of egg allergy.J Allergy Clin Immunol. 2007; 120: 1413-1417Abstract Full Text Full Text PDF PubMed Scopus (452) Google Scholar, 25Levy Y. Segal N. Garty B. Danon Y.L. Lessons from the clinical course of IgE-mediated cow milk allergy in Israel.Pediatr Allergy Immunol. 2007; 18: 589-593Crossref PubMed Scopus (45) Google Scholar, 26Cohen A. Goldberg M. Levy B. Leshno M. Katz Y. Sesame food allergy and sensitization in children: the natural history and long-term follow-up.Pediatr Allergy Immunol. 2007; 18: 217-223Crossref PubMed Scopus (76) Google Scholar, 27Cantani A. Micera M. Natural history of cow’s milk allergy. An eight-year follow-up study in 115 atopic children.Eur Rev Med Pharmacol Sci. 2004; 8: 153-164PubMed Google ScholarTable IIIIncidence of acquired food tolerance over timeReference, year, countryStudy designFollow-up periodStudy populationSensitizing allergenOutcomeMain resultsPyziak et al,19Pyziak K. Kamer B. Natural history of IgE-dependent food allergy diagnosed in children during the first three years of life.Adv Med Sci. 2011; 56: 48-55Crossref PubMed Scopus (15) Google Scholar 2011, PolandProspectiveMinimum 5 y83 children with food allergy (including food and food-inhalant allergy) diagnosed during first 3 y of lifeMilk, egg, soy, pork, beefIncidence of acquired food tolerance: overall, according to type of allergy (food/food-inhalant allergy), type of allergen, disease beginning timeOverall incidence, 87.9%; incidence in food group, 95.5%; incidence in food-inhalant group, 78.9% (P < .05); no statistically significant difference in incidence according to allergen type. Tolerance is acquired more quickly in children affected by milk allergy (more than half acquiring tolerance after the third year of life) compared with other allergens acquiring tolerance after the fourth or fifth (beef) year of life. Children affected since the first year of life had significantly lower ability to obtain tolerance than children affected since the third year of life (P < .05).Savage et al,22Savage J.H. Kaeding A.J. Matsui E.C. Wood R.A. The natural history of soy allergy.J Allergy Clin Immunol. 2010; 125: 683-686Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar 2010, United StatesRetrospectiveMedian 5 y133 children (male, 72%) with history of allergic reaction to soy; median age at initial visit: 1 ySoyIncidence of acquired food tolerance over time (Kaplan-Meier analysis)Kaplan-Meier analysis predicted resolution of soy allergy in 25% by age 4 y, 45% by age 6 y, and 69% by age 10 y. By age 6 y, 59% of children with a peak soy IgE level of 50 kU/L had outgrown soy allergy (P < .01 for trend).Keet et al,23Keet C.A. Matsui E.C. Dhillon G. Lenehan P. Paterakis M. Wood R.A. The natural history of wheat allergy.Ann Allergy Asthma Immunol. 2009; 102: 410-415Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar 2009, United StatesRetrospective31 mo103 children ≤18 y with clinical history of allergic reaction to wheat and positive wheat IgE testWheatDevelopment of oral tolerance to wheatMedian age of tolerance was 79 mo (IQR, 42-190 mo). Twenty-nine percent achieved tolerance by age 4 y (95% CI, 19% to 43%), 45% by age 6 y (95% CI, 34% to 59%), 56% by age 8 y (95% CI, 43% to 69%), 62% by age 10 y (95% CI, 48% to 75%), 65% by age 12 y (95% CI, 51% to 78%), and 70% by age 14 y (95% CI, 55% to 84%).Savage et al,24Savage J.H. Matsui E.C. Skripak J.M. Wood R.A. The natural history of egg allergy.J Allergy Clin Immunol. 2007; 120: 1413-1417Abstract Full Text Full Text PDF PubMed Scopus (452) Google Scholar 2007, United StatesRetrospectiveMedian 4.9 y881 children (male, 68%) with history of allergic reaction to eggs; median age at initial visit: 14 moEggIncidence of acquired food tolerance over time (Kaplan-Meier analysis)Kaplan-Meier analysis predicted resolution in 4% of patients with egg allergy by age 4 y, 12% by age 6 y, 37% by age 10 y, and 68% by age 16 y. Patients with persistent egg allergy had higher egg IgE levels at all ages to age 18 y. A patient’s highest recorded egg IgE level, presence of other atopic diseases, and presence of other food allergies were significantly related to egg allergy persistence.Levy et al,25Levy Y. Segal N. Garty B. Danon Y.L. Lessons from the clinical course of IgE-mediated cow milk allergy in Israel.Pediatr Allergy Immunol. 2007; 18: 589-593Crossref PubMed Scopus (45) Google Scholar 2007, IsraelProspectiveTransient CMA: mean duration of follow-up, 2.71 ± 2.24 y; persistent CMA: mean duration of follow-up, 5.13 ± 3.88 y43 children with transient CMA (age range, 0.48-11 y) and 62 patients with persistent CMA (age range, 3-16.5 y).Cow’s milkIncidence of acquired food tolerance; incidence of additional allergic diseases; symptoms and signs in both groupsOf the 43 patients with transient CMA, 20 children achieved tolerance to milk up to age 3 y, 13 up to age of 5 y, 7 up to age 9 y, and 3 up to age of 11 y. None of the patients in the persistent CMA group achieved tolerance. Patients with persistent CMA had a higher rate of asthma than patients with transient CMA (61.2% vs 18.6%, P < .001). Fifty patients with persistent CMA had 137 subsequent allergic reactions after diagnosis, 25% of the reactions were due to oral milk challenge at the clinic and 75% were due to accidental exposure, of which 13% required an emergency department visit and 8% required hospitalization.Skripak et al,21Skripak J.M. Matsui E.C. Mudd K. Wood R.A. The natural history of IgE-mediated cow’s milk allergy.J Allergy Clin Immunol. 2007; 120: 1172-1177Abstract Full Text Full Text PDF PubMed Scopus (592) Google Scholar 2007, United StatesRetrospectiveMedian 5 y807 children (male, 65%) with IgE-mediated CMACow’s milkIncidence of acquired food tolerance over timeRates of resolution were 19% by age