The natural history of egg allergy in an observational cohort Scott H. Sicherer, MD,a* Robert A. Wood, MD,b* Brian P. Vickery, MD,c Stacie M. Jones, MD,d Andrew H. Liu, MD,e David M. Fleischer, MD,e Peter Dawson, PhD,f Lloyd Mayer, MD,a A. Wesley Burks, MD,c Alexander Grishin, PhD,a Donald Stablein, PhD,f and Hugh A. Sampson, MDa New York, NY, Baltimore and Rockville, Md, Chapel Hill, NC, Little Rock, Ark, and Denver, Colo (all P < .05). Numerous additional baseline clinical and demographic factors and laboratory assessments were not associated with resolution. Multivariate analysis identified baseline egg-specific IgE levels and initial reaction characteristics as strongly associated with resolution; a calculator to estimate resolution probabilities using these variables was established. Conclusions: In this cohort of infants with egg allergy, approximately one half had resolved over 74 months of follow-up. Baseline egg-specific IgE levels and initial reaction characteristics were important predictors of the likelihood of resolution. (J Allergy Clin Immunol 2014;133:492-9.) Background: There are few studies on the natural history of egg allergy, and most are single-site and nonlongitudinal and have not identified early predictors of outcomes. Objective: We sought to describe the natural course of egg allergy and to identify early prognostic markers. Methods: Children age 3 to 15 months were enrolled in a multicenter observational study with either (1) a convincing history of an immediate allergic reaction to egg, milk, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis and a positive SPT response to egg or milk. Children enrolled with a clinical history of egg allergy were followed longitudinally, and resolution was established based on successful ingestion. Results: The cohort with egg allergy consists of 213 children followed to a median age of 74 months. Egg allergy resolved in 105 (49.3%) children at a median age of 72 months. Factors that were most predictive of resolution included the following: initial reaction characteristics (isolated urticaria/angioedema vs other presentations), baseline egg-specific IgE level, egg SPT wheal size, atopic dermatitis severity, IgG4 level, and IL-4 response Allergy to egg is estimated to affect 0.5% to 2.5% of young children,1-4 with a recent estimate of up to 8.9% of infants reacting to raw egg in one study from Australia.5 Having an egg allergy or being sensitized to egg is associated with increased From athe Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York; bthe Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore; cthe Department of Pediatrics, University of North Carolina, Chapel Hill; dthe Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, Little Rock; ethe Department of Pediatrics, National Jewish Health, Denver; and fthe EMMES Corporation, Rockville. Deceased. *These authors contributed equally to this work. Supported by National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) grant U19AI066738 and U01AI066560. The project was also supported by grants UL1 TR-000154 (National Jewish), UL1 TR-000067 (Mount Sinai), UL1 TR-000039 (Arkansas), UL1 TR-000083 (University of North Carolina) and UL1 TR-000424 (Johns Hopkins) from the National Center for Research Resources (NCRR), a component of the NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Disclosure of potential conflict of interest: S. H. Sicherer has received research support from the National Institute of Allergy and Infectious Disease (NIAID), is a board member for the American Board of Allergy and Immunology, has consultant arrangements with Novartis and Food Allergy Research and Education, and receives royalties from UpToDate. R. A. Wood has consultant arrangements with the Asthma and Allergy Foundation of America, is employed by Johns Hopkins University, has received research support from the National Institutes of Health (NIH), and receives royalties from UpToDate. B. P. Vickery has received research and travel support from the NIH/NIAID. S. M. Jones is on the Medical Advisory Board for Food Allergy Research & Education; is a National Advisory Board member for St Louis Children’s Hospital Food Allergy Management and Education; has consulted for the Gerson Lehrman Group; has received research support from the NIH, Food Allergy Research & Education, and the National Peanut Board; has a pending grant from the Department of Defense; has received payment for lectures from Abbott Nutrition International, the Kentucky Society for Allergy, Asthma & Immunology, the New England Allergy Society, the American College of Allergy, Asthma & Immunology, Indiana University Medical School and Riley Children’s Hospital, the Spanish Society of Allergy & Clinical Immunology, the Oregon Allergy, Asthma & Immunology Society, and the European Academy of Allergology and Clinical Immunology; has received payment for manuscript preparation from the American Academy of Allergy, Asthma & Immunology; and is on the Arkansas Medicaid Drug Review Committee. D. M. Fleischer has received research support from the NIH/NIAID and Monsanto, has consultant arrangements with Sanofi-Aventis, is employed by National Jewish Health, receives royalties from UpToDate, and has received payment for the development of educational presentations from the American Academy of Pediatrics Symposium 2013. P. Dawson has received research support from the NIH. A. W. Burks has received research support from the NIH, the Wallace Research Foundation, and Hycor Biomedical; has board memberships with the Academy of Allergy, Asthma & Immunology, the Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section of the NIH, the Food and Drug Administration Food Advisory committee, the Food Allergy & Anaphylaxis Network Research Advisory Board, and the Merck US Allergy Immunotherapy Allergist Advisory Board; has consultant arrangements with Dow AgroSciences, McNeill Nutritionals, Merck, Novartis Pharma AG, Sanofi Aventis US, Schering Plough, Unilever, ExploraMed Development, GLG Research, and Regeneron Pharmaceuticals; is employed by UNC Children’s Hospital; has a pending grant from Food Allergy Research and Education; has received payment for lectures from Abbott Laboratories, Mylan Specialty, and the American College of Allergy, Asthma & Immunology; has various US patents related to peanut allergens and methods; has received payment for development of educational presentations from Current Views 2012; and is a minority stockholder in Allertein and Mastcell Pharmaceuticals. A. Grishin has consultant arrangements with Allertein Therapeutics. D. Stablein has received research support from the NIH. H. A. Sampson has received research support from the NIAID, the NIH, and Food Allergy Research Education; is Chair of the PhARF Award review committee; has consultant arrangements with Allertein Therapeutics, Regeneron, and the Danone Research Institute; has received payment for lectures from Thermo Fisher Scientific, UCB, and Pfizer. The rest of the authors declare that they have no relevant conflicts of interest. Received for publication August 28, 2013; revised November 1, 2013; accepted for publication December 6, 2013. Corresponding author: Scott H. Sicherer, MD, Division of Allergy/Immunology, Mount Sinai Hospital, Box 1198, One Gustave L. Levy Place, New York, NY 10029-6574. E-mail: scott.sicherer@mssm.edu. 0091-6749/$36.00 Ó 2014 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaci.2013.12.1041 492 Key words: Egg allergy, natural history, food allergy, IgE SICHERER ET AL 493 J ALLERGY CLIN IMMUNOL VOLUME 133, NUMBER 2 Abbreviations used AD: Atopic dermatitis CoFAR: Consortium of Food Allergy Research Ct: Cycle threshold HR: Hazard ratio OFC: Oral food challenge SPT: Skin prick test risk of peanut and other food allergies, atopic dermatitis (AD), and development of respiratory allergies and asthma.6-9 For those with egg allergy, avoidance is difficult, and allergic reactions from accidental ingestion are common.10 Fortunately, egg allergy typically resolves during childhood.11-14 However, the rate of resolution might be slowing, with a past study suggesting the majority are egg tolerant by age 3 years13 and a recent study suggesting about half of children reach tolerance by age 12 years.11 The recent study from a referral population showed persistent egg allergy for 42% of children in late adolescence,11 suggesting the number of adults with egg allergy might increase with time, although the current estimate of egg allergy among adults is 0.2%.9 The ability to determine the prognosis of egg allergy is critical because potential interventions under study carry risks15 and ideally would be applied in those unlikely to achieve resolution naturally. The Consortium of Food Allergy Research (CoFAR) enrolled 512 infants with likely egg or milk allergy but without previously known peanut allergy in a multicenter observational study to address the immunologic, genetic, and environmental factors that affect the natural course of food allergy.16,17 Evaluations were offered every 6 months, and oral food challenges (OFCs) were offered as clinically indicated, similarly to the studies described above.11-14 We previously reported the natural course of milk allergy in this cohort and identified a number of prognostic markers that could be used to estimate resolution rates using baseline characteristics.18 The primary aim of the current analysis is to assess the natural history of egg allergy in the infants enrolled in this cohort, with a focus on the clinical factors predicting the resolution of egg allergy over the first 6 years of life. METHODS Subjects, study definitions, and procedures The subjects of this study are a subset with egg allergy of a larger cohort of 512 infants originally enrolled at 3 to 15 months of age at 5 sites (children with egg allergy/total enrolled per site): the Icahn School of Medicine at Mount Sinai, New York (47/106); Duke University Medical Center, Durham, North Carolina (now followed at the University of North Carolina, 20/103); Johns Hopkins University School of Medicine, Baltimore, Maryland (37/109); National Jewish Health, Denver, Colorado (42/99); and Arkansas Children’s Hospital, Little Rock, Arkansas (67/95), as described previously.16,18 Enrollment criteria for the whole cohort were designed to include atopic children with likely egg or milk allergy at risk of peanut allergy but without current peanut allergy. Briefly, enrollment required either (1) a history of a convincing immediate allergic reaction to egg, cow’s milk, or both and a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe AD and a positive SPT response to egg, milk, or both. Exclusion criteria included clinical evidence of peanut allergy or a peanut-specific IgE level of greater than 5 kUA/L identified before enrollment.16,18 The subgroup of children in the current study had a diagnosis of egg allergy at the time of enrollment or acquired this diagnosis after enrollment with no prior evidence of egg tolerance. Study procedures were reviewed and approved by the National Institutes of Allergy and Infectious Diseases Data Safety Monitoring Board and by local institutional review boards, and written signed consent forms were obtained. Participants were considered to have egg allergy if their initial reaction was either (1) a positive physician-supervised OFC result; (2) a convincing reaction (defined by symptoms within an hour of isolated ingestion that included at least urticaria and/or angioedema, difficulty breathing, wheezing, throat tightness, and/or vomiting) and sensitization to egg (egg-specific IgE > _0.35 kUA/L and/or SPT response >3 mm); or (3) a flare of AD associated with egg ingestion and an egg-specific IgE level of greater than 2 kUA/L, a level that is greater than 95% predictive of egg allergy in infants.13 Reaction details were recorded regarding skin, oral, respiratory, gastrointestinal, and cardiovascular symptoms. The study analyzed 3 mutually exclusive initial clinical presentations of reaction to egg ingestion: AD diagnosis (flare of AD), skin-only reactions (acute hives and/or angioedema), or systemic reactions (eg, more than isolated skin reactions, including respiratory and gastrointestinal reactions). Subjects were considered egg tolerant if they ingested whole concentrated egg products (scrambled egg or French toast) in serving size quantities without symptoms either during physician-supervised OFCs or after introduction at home. Dietary ingestion of products with extensively heated egg (baked egg, for example as an ingredient in a muffin or cookie) was queried but was not considered evidence of resolved egg allergy. Dietary, medical, and social histories were obtained by using questionnaires completed during enrollment interviews. A diagnosis of asthma and allergic rhinitis was based on parental report or parental report of a physician’s diagnosis. A diagnosis of other food allergies included per-protocol definitions for egg and peanut,16,18 whereas for other foods, this was based on a clinical diagnosis by a study physician. Diagnosis of baseline AD, in distinction to the AD flares caused by egg ingestion described above, required pruritus and an eczematous rash (acute, subacute, or chronic) with typical morphology and age-specific patterns, a chronic or relapsing history, atopy (personal and/or family history or IgE reactivity), and xerosis. AD severity was graded based on criteria previously described and published by Rajka and Langeland.19 Briefly, the AD severity was graded as mild, moderate, or severe (see Table E1 in this article’s Online Repository at www.jacionline.org), as described previously.18 Atopic disease history in parents of the enrolled infants was based on previously published definitions and was recorded by parental report.20 To maintain uniformity and an observational approach, the study design includes evaluations, care for food allergy, and instructions on dietary management that were uniform among the clinical centers and reflect practice parameters in force at the time of enrollment for AD,21 food allergy,22 and allergy prevention.23 Participants were evaluated in person at enrollment, 6 months, 12 months, and yearly thereafter, with additional telephone followup between each visit and instructions to contact the study site for any allergic reactions, at which time additional details were obtained.10 OFCs to egg were typically offered when egg-specific IgE serum concentrations were less than 2 kUA/L and the mean skin test wheal diameter was less than 10 mm if there was no reaction in the preceding 6 months. However, OFCs were not withheld if additional clinical data warranted OFCs outside of these parameters (eg, tolerance of a small accidental exposure or parental preference). OFC results were considered positive for persistent subjective or objective symptoms.24 OFCs were performed with cooked whole or pasteurized powdered egg but not raw egg white. SPTs SPTs were performed by using the GreerPick (Greer Laboratories, Lenoir, NC), with participants avoiding antihistamines for at least 5 half-lives of the specific agent. Tests were performed on the infant’s back, and at 15 minutes, the wheal was outlined in pen and transferred by tape to paper. The sizes of the longest diameter and its longest perpendicular were averaged. An SPT score was computed by subtracting the saline control measure, and a positive SPT response is defined by a score of 3 mm or greater. Tests were considered reliable if the wheal size of the negative control (50% glycerin-saline) was 3 mm or smaller and the wheal size of the histamine control was at least 3 mm larger than the wheal size of the negative control. All sites used the same lot of 494 SICHERER ET AL reagents, and training was performed to ensure consistency. The egg (chicken) white extract was obtained from Greer Laboratories (catalog no. F272). J ALLERGY CLIN IMMUNOL FEBRUARY 2014 TABLE I. Baseline characteristics Egg allergy resolved No Serum egg-specific IgE and IgG4 levels The concentration of specific IgE antibody to egg white was measured from plasma at a central laboratory (Mount Sinai) by using the Thermo Fisher ImmunoCAP system (Thermo Fisher, Uppsala, Sweden) and reported in kilounits of antigen per liter. A level of greater than 0.35 kUA/L was considered positive. The concentration of IgG4 antibodies to milk were also measured from plasma samples by using the ImmunoCAP system (detection limit, 0.07 mg/L). Mononuclear cell stimulation and PCR analysis Studies were performed to determine whether egg-specific TH2 or regulatory T-cell gene expression was predictive of egg allergy outcomes. PBMC isolation was performed by using Ficoll-Paque density gradient centrifugation, and cultures were performed at each clinical site on fresh venous blood samples, as previously described.16 Briefly, 4 million cells per condition were cultured for 48 hours in AIM-V serum-free media (Invitrogen, Carlsbad, Calif) with egg white protein (50 mg each/mL), aqueous peanut extract (50 mg/mL), tetanus toxoid (5 mg/mL), and purified a-, b-, and k-caseins (50 mg each/mL), and additional control stimulations were performed with medium alone (negative) and anti-CD3/anti-CD28 beads (positive). At the end of the culture period, cells expressing CD25 were enriched by means of selection with anti-CD25–coated paramagnetic beads, according to the manufacturer’s protocol (Miltenyi Biotech, Bergisch Gladbach, Germany). Pilot experiments demonstrated approximately 10-fold enrichment of CD251 cells, with 70% to 80% of selected cells coexpressing CD3, CD4, and CD25, as measured by means of flow cytometry. The entire selected fraction of cells was immediately lysed in RLT buffer (Qiagen, Hilden, Germany) and stored at 2808C until RNA purification. The quantitative PCR was carried out in the central laboratory according to the in-house established protocol by using SYBR Green I fluorescence detection in a 384-well plate on ABI 7900 (Applied Biosystems, Foster City, Calif). Raw PCR analysis and annotation were performed on coded samples. The cycle threshold (Ct) number was set by software with confirmation and adjustment as necessary to define the threshold of linear amplification. For the gene expression data, DDCt was calculated by subtracting the RPS9 reporter gene Ct and then normalizing by subtracting the standardized medium control response. Negative values indicate relatively higher activity, with a unit score change corresponding to a doubling. Nondetected genes were arbitrarily assigned a Ct of 40. Statistical analysis Time to resolution of egg allergy was measured with age as the time metric whether enrolled with egg allergy or having the diagnosis after enrollment. Although the time of allergy diagnosis varied depending on when food introduction and diagnostic testing were performed, each subject’s first definitive diagnosis was positive for egg allergy. Proportional hazards regression models were fit to examine covariates for their effect on the hazard or risk function.25 The estimated survival distribution was calculated from the relative hazard, which is the exponentiated sum of the linear combination of the products of the parameter estimates with their respective clinical characteristics. The common underlying empiric cumulative hazard function Lambda(t) is estimated with a step function, and the resolution curve is estimated as follows: 12expð2RH  Lambda½tÞ: In this article hazard refers to the chance of a beneficial event (ie, allergy resolution), and variables are structured so that large relative hazard values are associated with increased chance of allergy resolution. A multivariate proportional hazards model was fit by using significant baseline factors from the univariate models to assess the probability of allergy resolution over time. The final model was selected based on factor significance and model fit. Time-varying clinical covariate analyses used the most recent available Total subjects Sex Female Male Race White Black/African American Asian Other Baseline egg IgE (kUA/mL)* _2.0-10.0 > _10.0 Reaction class AD diagnosis Skin only Other system Egg SPT wheal (mm)à 5 Baseline age (mo) 3-5 6-8 9-12 13-15 Baseline AD None Mild Moderate Severe Breast-feeding history Never Yes, currently Yes but no longer Other food allergy No Yes Baseline milk allergy Allergic Other Asthma/rhinitis No Yes Yes All (no.) No. Percent No. Percent 213 108 50.70 105 49.30 63 150 26 82 41.27 54.67 37 68 58.73 45.33 161 36 12 4 80 19 7 2 49.69 52.78 58.33 50.00 81 17 5 2 50.31 47.22 41.67 50.00 78 72 60 30 35 41 38.46 48.61 68.33 48 37 19 61.54 51.39 31.67 27 93 93 17 37 54 62.96 39.78 58.06 10 56 39 37.04 60.22 41.94 50 162 20 87 40.00 53.70 30 75 60.00 46.29 13 32 88 80 8 14 48 38 61.54 43.75 54.55 47.50 5 18 40 42 38.46 56.25 45.45 52.50 17 31 104 61 9 11 52 36 52.94 35.48 50.00 59.02 8 20 52 25 47.06 64.52 50.00 40.98 40 57 116 22 29 57 55.00 50.88 49.14 18 28 59 45.00 49.12 50.86 103 110 49 59 47.57 53.64 54 51 52.43 46.36 91 122 48 60 52.75 49.18 43 62 47.25 50.82 169 44 89 19 52.66 43.18 80 25 47.34 56.82 *Three participants had missing baseline egg-specific IgE values. The mutually exclusive clinical presentation of the initial reaction to egg ingestion was categorized as follows: AD diagnosis (flare of AD; this category included egg-specific IgE >2 kUA/L), skin-only reactions (acute hives and/or angioedema), or systemic reactions (eg, more than isolated skin, including respiratory and gastrointestinal reactions). àOne subject had missing baseline egg SPT values. assessment in the model, and nonproportional hazards were examined by fitting linear and spline function interactions with time. Reported P values are 2-tailed when applicable, and SAS 9.2 (SAS Institute, Cary, NC) and R software were used for the computations. RESULTS Of the 512 enrolled infants, the cohort with egg allergy consisted of 213 children, of whom 140 were given a diagnosis of egg allergy at baseline. In the remaining 73 children, the SICHERER ET AL 495 J ALLERGY CLIN IMMUNOL VOLUME 133, NUMBER 2 FIG 1. Kaplan-Meier analysis of egg allergy resolution over time with pointwise 95% CIs. diagnosis was categorized as uncertain at the entry visit, but egg allergy was subsequently confirmed at a median age of 23.2 months (interquartile range, 16.1-41.9 months), 10 based on OFC results. Key baseline characteristics are summarized in Table I and Table E2 in this article’s Online Repository at www. jacionline.org. AD was present in 196 and categorized as mild in 31, moderate in 104, and severe in 61. Twenty-seven (12.7%) infants were given diagnoses of egg allergy based on AD criteria, whereas the remainder had a history of an acute reaction and positive test results. Ninety-three subjects were first given a diagnosis based on a reaction or clinical history that was limited to skin symptoms (hives, pruritus, or swelling) after exposure. Another 93 subjects were given a diagnosis based on a reaction that involved more extensive symptoms (eg, oral, upper/lower respiratory, gastrointestinal, or cardiovascular) in addition to or apart from urticaria/angioedema. One hundred five (49.3%) of the 213 participants have now resolved their egg allergy, with a median age of resolution of 72 months and a median age at last follow-up of 74 months (Fig 1). Resolution was defined based on OFC results in 47 (44.8%) and by successful home introduction of whole (not baked) egg products in the remainder recorded by the time of their visit. Regarding exposure to egg in baked goods, at the 6-year time point, 43 (38.1%) of 113 subjects with unresolved allergy reported tolerating at least some baked egg products, whereas 4 reported reactions to ingestion of baked egg products. Additional baseline characteristics of the cohort, comparing those with and without egg allergy resolution, are presented in Table I, and Cox regression analyses are shown in Table II. The baseline characteristics that were most predictive of egg allergy resolution included egg-specific IgE levels and the characteristics of the presenting reaction. Specifically, highly significant differences (P < .001) in the rate of resolution were noted when comparing those subjects with baseline egg-specific IgE levels of less than 2 kUA/L, 2 to 10 kUA/L, and 10 kUA/L or greater (Fig 2). Significant differences (P 5 .007) in resolution were also predicted by reaction classification, with those having acute reactions with only skin symptoms having a greater likelihood of resolution compared with those with acute reactions involving systems beyond the skin (Fig 3, distinguishing the 3 clinical categories described above). Those with an AD flare from egg and those with systemic reactions to egg had poorer prognosis than those with isolated urticaria/angioedema. The poor prognosis of the former reaction category might be partly influenced by the requirement for increased egg-specific IgE antibody levels in the definition of an egg-induced allergic reaction manifested by an AD flare. Resolution was also associated with baseline AD severity (Table II and see Fig E1 in this article’s Online Repository at www.jacionline.org), egg SPT responses (Table II and see Fig E2 in this article’s Online Repository at www.jacionline.org), and egg-specific IgG4 levels (Table II and see Fig E3 in this article’s Online Repository at www.jacionline.org), although only weakly. Only 18 (17.1%) of the subjects with resolved egg allergy reported no AD at the time of resolution. Additional factors that correlated with rapidity of resolution included sex, T-cell responses (see below), and the egg-specific IgE/IgG4 ratio (hazard ratio [HR], 0.62; 95% CI, 0.47-0.82; P < .001), although this latter effect appears to be a result of the strong correlation (Spearman r 5 0.63) with egg-specific IgE levels. Parameters not associated with resolution included race, breast-feeding, other food allergies, baseline milk allergy diagnosis, asthma or rhinitis, family income, parental education, presence of siblings, and parental atopy. Although baseline milk allergy was not related to egg allergy resolution, when resolution of milk allergy was examined as a time-varying covariate, it was associated with egg allergy resolution, and the effect persisted when adjusted for log egg IgE levels and skin reaction classification (data not shown). Not surprisingly, baked egg (eg, in muffins and cookies) consumption was related to resolution outcomes.26 Egg allergy resolution rates were 75 (45.2%) of 166, 8 (57.1%) of 14, and 17 (70.8%) of 24 among the 204 subjects reporting no baked egg consumption, baked egg consumption with a reaction, and baked egg consumption without a reaction at the 6-month follow-up visit. The instantaneous risk ratios for resolution are 1.8 and 3.4 for the latter classes versus the nonconsumption group; the difference is statistically significant (P < .001) and is maintained after adjustment for log IgE levels and skin reaction classification. At 6 years of age, baseline characteristics, 496 SICHERER ET AL J ALLERGY CLIN IMMUNOL FEBRUARY 2014 TABLE II. Resolution of egg allergy (Cox regression analysis with 1 variable in the model at a time) Risk factor for resolution of egg allergy Baseline egg-specific IgE (kUA/L) _10 _10 2-10 vs > Baseline egg SPT wheal (mm) _10 _10 5- Baseline egg-specific IgG4 (mgA/L) 0.4 0.10-0.40 vs >0.4 Baseline age (mo) 3-5 vs 13-15 6-8 vs 13-15 9-12 vs 13-15 Sex Female vs male Race White vs nonwhite Baseline AD None/mild vs moderate/severe Breast-feeding Yes but no longer vs never Yes, currently vs never Other food allergy Yes vs no Asthma or rhinitis Yes vs no Reaction class Skin only vs systemic AD diagnosis vs systemic HR* 95% HR confidence limits 3.874 2.064 2.25-6.66 1.19-3.59 2 kUA/L), skin-only reactions (acute hives and/or angioedema), or systemic reactions (eg, more than isolated skin, including respiratory and gastrointestinal reactions). expected higher IgG4 levels to predict resolution, as observed in immunotherapy treatment trials,15 but we saw the opposite, which might indicate a difference in mechanisms between natural tolerance and desensitization induced by immunotherapy. Eggspecific IgG4 levels increase with exposure, and the lower values in those who later had tolerance could simply reflect earlier careful avoidance of larger exposures. Nonetheless, the relationship of IgG4 levels to outcomes was weak and not significant in multivariate analysis. Regarding ingestion of baked egg, we did not mandate exposure in this observational study and did not begin to monitor baked egg ingestion until after baseline visits. Although eventual ingestion of baked egg was associated with resolution, this outcome could reflect a milder phenotype prone to resolution, an immunotherapeutic benefit, or a phenomenon related to accelerated testing with whole-egg exposure after successful ingestion of baked egg. The distinctions are not evaluable in the present study design. Interestingly, among those with persistent allergy, exposure to baked egg products was not predicted by baseline characteristics. T-cell stimulation studies identified several markers associated with the natural course of egg allergy in our cohort. We found reduced expression of egg-specific IL4 mRNA to be associated with resolution, which is consistent with a prior report.35 The subgroup evaluated here (those with egg allergy evaluated prospectively for resolution) are distinct from the entire cohort in which we reported no IL-4 signal, distinguishing those with 498 SICHERER ET AL or without baseline egg allergy/sensitization,16 which might account for the different results. Nonetheless, the IL-4 signal P value was marginal and not a strong contributor to the predictive models. However, a number of IL-4 responses to other stimulants were also associated with egg allergy prognosis, possibly reflecting a more generalized immune reactivity as a marker of resolution. Ultimately, these cellular studies did not contribute substantially to predicting outcomes. Overall, our study has identified a number of factors that predict egg allergy outcomes, confirming a number of factors identified previously and uniquely providing the opportunity to use our large multicenter cohort to evaluate the most relevant baseline factors. The substantial predictive capacity of egg-specific IgE levels and clinical presentation allowed for the development of a novel algorithm to estimate the natural course of egg allergy. This composite index has been developed into an equation that can be applied to young (36% BSA >3 mo remission in past year (>25% lifetime in remission for age .05 for all comparisons, Fisher exact test). Acoustic rhinometry was performed in 13 children: no significant change in minimal cross-sectional area of the nasal airway (suggestive of nasal congestion) was observed (median change in nasal patency, 25.3%; IQR, 218.7% to 18.6%; P 5 .97, Wilcoxon signed-rank test). None of these children reported nasal symptoms. Delayed adverse events after immunization After excluding events in 7 patients that were deemed unrelated or unlikely to be related to vaccination by the independent data monitoring committee, 73 (of 278) children had delayed events (occurring between 2 and 72 hours after vaccine administration) reported after the first dose, and 35 (of 148) had delayed events after the second dose. Across both doses, 91 children had a delayed event after at least 1 dose of LAIV. The delayed events are summarized in Table I. Twenty-six (9.4%; 95% CI for population, 6.2% to 13.4%) children experienced lower respiratory tract symptoms within 72 hours, including 13 (4.7%; 95% CI for population, 2,5% to 7.9%) children with parent-reported wheeze. Children with a diagnosis of recurrent wheeze or asthma were not more likely to experience any adverse events than those without (59/186 [32%] vs 32/92 [35%], respectively; P 5 .68) or wheeze/cough (18/186 [10%] vs 8/92 [9%], P 5 1.00) after LAIV administration. Wheeze/cough was not more common in children receiving regular inhaled corticosteroid (BTS/SIGN step 2 therapy or greater, P 5 .55). Medical review by the child’s primary care physician was sought in 2 cases, but no change in medication or treatment resulted. No child presented to the hospital because of a reported adverse event within 72 hours. No serious adverse events reported during the study were attributable to LAIV administration. In the 148 children who received 2 doses of LAIVand in whom follow-up was complete, 20 (13.5%) were reported to have 380 TURNER ET AL experienced an adverse event after immunization within 72 hours for both doses. In only 4 cases were symptoms similar in both reactions, and in 2 of 4 cases the reported adverse event after immunization was an eczema flare. DISCUSSION In this highly atopic cohort of children with egg allergy, there were no systemic allergic reactions or episodes of anaphylaxis after administration of LAIV. This equates to an upper 95% CI of 1.3% for the incidence of an acute systemic allergic reaction for children with egg allergy in the population. Des Roches et al25 recently reported a cohort of 68 children with a diagnosis of egg allergy who received LAIV without an allergic reaction; however, the criteria used to define egg allergy in their cohort were less stringent than in the current study, and thus a proportion of the children reported in that study might have no longer been clinically allergic to egg. The rate observed for attributable allergic reactions after vaccine (2.8%) is higher than previously reported.10 These reactions were all mild, localized, and self-limiting. Safety data from postmarketing surveillance in the United States has shown LAIV to be a well-tolerated vaccine.12-14,26 Baxter et al14 reported 9 episodes of urticaria occurring within 3 days of LAIV administration in children aged 5 to 17 years of 43,702 doses administered during the period 2003-2008. However, it is unclear how many of these episodes occurred within 2 hours of LAIV administration, which is consistent with an IgE-mediated mechanism caused by LAIV. In a further surveillance study of 2.5 million doses of LAIV in adults, 7 cases of systemic allergic reactions (anaphylaxis) occurred, which is equivalent to a rate of 0.3 reactions per 100,000 doses; none were related to egg allergy, and only 5 were deemed to be causally related to LAIV administration.27 A randomized, double-blind, placebo-controlled trial of the safety of LAIV in children aged 6 to 59 months without egg allergy reported that the most common adverse event was rhinorrhea/nasal congestion.10 This has been subsequently confirmed in postmarketing surveillance studies.27 Despite the high rate of atopy in our cohort, the rates of adverse events were similar to those previously reported (Table II).10 In this study children with asthma (including those using preventer therapy) or recurrent wheeze were not at greater risk of parent-reported wheeze in the 72 hours after LAIV administration. It was not possible to compare rates of wheeze with those of previous studies because the latter refer to ‘‘medically significant wheeze’’ diagnosed by a health care professional occurring up to 42 days after vaccine administration; unfortunately, rates of parent-reported lower respiratory tract symptoms in the days after LAIV have not been assessed in prior studies. Furthermore, children requiring higher levels of asthma treatment (BTS step 3 or greater) were not at higher risk of parent-reported wheeze, a group that still constituted 25% of our cohort. A report of 2 randomized multinational trials comparing LAIV with IIV in 1940 children aged 2 to 5 years with asthma or a history of wheezing found no difference between the incidence of wheezing after vaccination between those who received LAIV and IIV.8 The rates of lower respiratory tract symptoms ranged from 5% to 29.9% (any wheeze within 42 days of vaccine administration) and are similar to our study. Other studies in older children have likewise found no evidence for an increase in J ALLERGY CLIN IMMUNOL AUGUST 2015 asthma exacerbation or medically significant wheeze after LAIV compared with IIV.9,16 It is clear that wheeze is a relatively common symptom in this group of children. In contrast to UK guidance, guidelines in the Unites States and Canada currently recommend against the use of LAIV in children with asthma, although this advice was recently been revised, permitting the use of LAIV in children aged 2 to 4 years without symptoms of wheezing in the 12 months before vaccination.6 We found no evidence for an increase in ‘‘medically significant wheezing’’ after LAIV in those children with a history of recurrent wheeze or asthma. We are unable to determine whether the episodes of wheezing observed would have occurred in the absence of LAIV immunization. Analysis of the 4 batches of LAIV used during this study for the Department of Health, England, found the maximum concentration of ovalbumin present to be less than 0.3 ng/mL. However, the egg protein content of influenza vaccine varies between batches, and our data might not be applicable to future stocks of LAIV in which the egg content of the vaccine might be higher.28,29 The maximum level of ovalbumin permitted in LAIV under the license granted by the European Medicines Agency is 1.2 mg/mL30; this is approximately 10 times lower than the amount of egg protein found to trigger local rhinitis symptoms when administered into the nasal airways of children with egg allergy.31 Therefore it is unlikely that LAIV would be expected to trigger symptoms because of an IgE-mediated allergic reaction to egg. In summary, these data have demonstrated a safety profile in terms of systemic allergic reactions to LAIV (supplied during the 2013-2014 influenza season) in children with egg allergy, including those with a prior history of anaphylaxis, similar to that previously reported for children without egg allergy. Furthermore, the vaccine appears to be well tolerated in children with a diagnosis of asthma or recurrent wheeze. We thank our data monitoring committee (Glenis Scadding [Chair], Andrew Riordan, Giuseppina Rotiroti, and Andre Charlett), as well as members of our Trial Steering Committee (Nicola Brathwaite [Chair], Diab Haddad, and Hazel Gowland). We also thank our coinvestigators in the SNIFFLE study team and the UK Paediatric Vaccine Group for their support, as well as PHE colleagues for their support in data management: Samuel Lattimore, Deborah Cohen, Rashmi Malkani, and Teresa Gibbs. The SNIFFLE Study Investigators are: Christine Doyle (Alder Hey Children’s NHS Foundation Trust), George Du Toit (NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust), Michel Erlewyn-Lajeunesse (University Hospital Southampton NHS Foundation Trust), Roisin Fitzsimons (NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust), Paul T. Heath (Institute of Infection and Immunity, St George’s University of London), Stephen M. Hughes (Central Manchester University Hospitals NHS Foundation Trust), Louise Michaelis (Great North Children’s Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust), J€urgen Schwarze (University of Edinburgh and NHS Lothian), Matthew D. Snape (NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Trust), Gary Stiefel (University Hospitals of Leicester NHS Trust), Huw M. Thomas (University Hospitals Bristol NHS Foundation Trust), and Paul J. Turner (NIHR/Imperial Biomedical Research Centre and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London). Clinical implications: Influenza vaccination with LAIV was safe in children with egg allergy, including those with a prior history of anaphylaxis, with no systemic allergic manifestations seen. TURNER ET AL 381 J ALLERGY CLIN IMMUNOL VOLUME 136, NUMBER 2 REFERENCES 1. Eggesbo M, Botten G, Halvorsen R, Magnus P. The prevalence of allergy to egg: a population-based study in young children. Allergy 2001;56:403-11. 2. Des Roches A, Paradis L, Gagnon R, Lemire C, Begin P, Carr S, et al. Egg-allergic patients can be safely vaccinated against influenza. J Allergy Clin Immunol 2012; 130:1213-6.e1. 3. Gagnon R, Primeau MN, Des Roches A, Lemire C, Kagan R, Carr S, et al. Safe vaccination of patients with egg allergy with an adjuvanted pandemic H1N1 vaccine. J Allergy Clin Immunol 2010;126:317-23. 4. Erlewyn-Lajeunesse M, Lucas JS, Warner JO. Influenza immunization in egg allergy: an update for the 2011-2012 season. Clin Exp Allergy 2011;41:1367-70. 5. Kelso JM, Greenhawt MJ, Li JT, Nicklas RA, Bernstein DI, Blessing-Moore J, et al. Adverse reactions to vaccines practice parameter 2012 update. J Allergy Clin Immunol 2012;130:25-43. 6. Grohskopf LA, Olsen SJ, Sokolow LZ, Bresee JS, Cox NJ, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP)—United States, 2014-15 Influenza Season. MMWR Morb Mortal Wkly Rep 2014;63:691-7. 7. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12:36-44. 8. Ambrose CS, Wu X, Knuf M, Wutzler P. The efficacy of intranasal live attenuated influenza vaccine in children 2 through 17 years of age: a meta-analysis of 8 randomized controlled studies. Vaccine 2012;30:886-92. 9. Fleming DM, Crovari P, Wahn U, Klemola T, Schlesinger Y, Langussis A, et al. Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma. Pediatr Infect Dis J 2006;25:860-9. 10. Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, et al. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 2007;356:685-96. 11. Ambrose CS, Dubovsky F, Yi T, Belshe RB, Ashkenazi S. The safety and efficacy of live attenuated influenza vaccine in young children with asthma or prior wheezing. Eur J Clin Microbiol Infect Dis 2012;31:2549-57. 12. Tennis P, Toback SL, Andrews E, McQuay LJ, Ambrose CS. A postmarketing evaluation of the frequency of use and safety of live attenuated influenza vaccine use in non-recommended children younger than 5 years. Vaccine 2011;29:4947-52. 13. Tennis P, Toback SL, Andrews EB, McQuay LJ, Ambrose CS. A US postmarketing evaluation of the frequency and safety of live attenuated influenza vaccine use in non-recommended children younger than 5 years: 2009-2010 season. Vaccine 2012;30:6099-102. 14. Baxter R, Toback SL, Sifakis F, Hansen J, Bartlett J, Aukes L, et al. A postmarketing evaluation of the safety of Ann Arbor strain live attenuated influenza vaccine in children 5 through 17 years of age. Vaccine 2012;30:2989-98. 15. Belshe RB, Ambrose CS, Yi T. Safety and efficacy of live attenuated influenza vaccine in children 2-7 years of age. Vaccine 2008;26(suppl 4):D10-6. 16. Gaglani MJ, Piedra PA, Riggs M, Herschler G, Fewlass C, Glezen WP. Safety of the intranasal, trivalent, live attenuated influenza vaccine (LAIV) in children 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. with intermittent wheezing in an open-label field trial. Pediatr Infect Dis J 2008; 27:444-52. Public Health England. Chapter 19: Influenza. In: Immunisation against infectious disease. Department of Health. Available at: https://www.gov.uk/government/ uploads/system/uploads/attachment_data/file/347458/Green_Book_Chapter_19_ v6_0.pdf. Accessed September 30, 2014. Hill DJ, Heine RG, Hosking CS. The diagnostic value of skin prick testing in children with food allergy. Pediatr Allergy Immunol 2004;15:435-41. World Allergy Organization guidelines for the assessment and management of anaphylaxis. WAO J 2011;4:13-37. British Thoracic Society and Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. Available at: https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/ btssign-asthma-guideline-2014/. Accessed September 30, 2014. Sampson HA, Gerth van Wijk R, Bindslev-Jensen C, Sicherer S, Teuber SS, Burks AW, et al. Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol 2012;130:1260-74. Bousquet PJ, Combescure C, Klossek JM, Daures JP, Bousquet J. Change in visual analog scale score in a pragmatic randomized cluster trial of allergic rhinitis. J Allergy Clin Immunol 2009;123:1349-54. Hilberg O. Objective measurement of nasal airway dimensions using acoustic rhinometry: methodological and clinical aspects. Allergy 2002; 57(suppl 70):5-39. Ruggeberg JU, Gold MS, Bayas JM, Blum MD, Bonhoeffer J, Friedlander S, et al. Anaphylaxis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2007;25:5675-84. Des Roches A, Samaan K, Graham F, Lacombe-Barrios J, Paradis J, Paradis L, et al. Safe vaccination of egg allergic patients with live attenuated influenza vaccine. J Allergy Clin Immunol Pract 2014;3:138-9. Toback SL, Ambrose CS, Eaton A, Hansen J, Aukes L, Lewis N, et al. A postlicensure evaluation of the safety of Ann Arbor strain live attenuated influenza vaccine in children 24-59 months of age. Vaccine 2013;31:1812-8. Izurieta HS, Haber P, Wise RP, Iskander J, Pratt D, Mink C, et al. Adverse events reported following live, cold-adapted, intranasal influenza vaccine. JAMA 2005; 294:2720-5. Goldis ME, Bardina L, Gimenez G, Lin J, Sampson HA. Evaluation of flu vaccines with regard to their egg protein content. Pediatr Allergy Immunol 2011;22:642-3. McKinney KK, Webb L, Petersen M, Nelson M, Laubach S. Ovalbumin content of 2010-2011 influenza vaccines. J Allergy Clin Immunol 2011;127:1629-32. Fluenz Tetra—summary of product characteristics. Available at: http://www. medicines.org.uk/emc/medicine/29112. Accessed September 30, 2014. Turner PJ, Erlewyn-Lajeuness M. Egg Protein in the intranasal liveattenuated influenza vaccine (LAIV) is unlikely to cause egg-mediated allergic reactions in egg-allergic children. J Allergy Clin Immunol Pract 2015;136:376-81. Food Allergy NIAID An Overview National Institute of Allergy and Infectious Diseases U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health NIAID HEALTH INFORMATION National Institute of Allergy and Infectious Diseases Food Allergy An Overview U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases NIH Publication No. 11-5518 November 2010 www.niaid.nih.gov 3 Introduction 4 What Is Food Allergy? 5 What Is an Allergic Reaction to Food? 8 What Is Anaphylaxis? 10 Common Food Allergies in Infants, Children, and Adults 12 Milk Allergy in Infants and Children 14 Is It Food Allergy or Food Intolerance? 17 Diagnosing Food Allergy 22 Preventing and Treating Food Allergy 24 Food Allergy Research at NIAID 26 Glossary 29 More Information 33 Credits NIAID I FOOD ALLERGY Contents 1 Introduction All of us eat to survive, and most of us enjoy eating. However, recent studies have found that almost 1 in 20 young children under the age of 5 years and almost 1 in 25 adults are allergic to at least one food. Other studies indicate that food allergy, especially allergy to peanut, is on the rise. As a result, more and more people are becoming aware of food allergy, making it a subject of increasing public concern. When one person in a family has a food allergy, the whole family is affected. There may be day-to-day anxiety that a loved one may accidentally eat a food that could lead to anaphylaxis, a dangerous allergic reaction. This booklet will help you understand allergic reactions to foods and their possible causes, and it explains how a healthcare professional diagnoses and treats food allergy. If you suspect you or a member of your family have a food allergy, consult your healthcare professional for medical advice. NIAID I FOOD ALLERGY Note: Words in bold are defined in the glossary at the end of this booklet. 3 What Is Food Allergy? Food allergy is an abnormal response to a food triggered by the body’s immune system. There are several types of immune responses to food. This booklet focuses on one type of adverse reaction to food—that in which the body produces a specific type of antibody called immunoglobulin E (IgE). The binding of IgE to specific molecules present in a food triggers the immune response. The response may be mild or in rare cases it can be associated with the severe and lifethreatening reaction called anaphylaxis, which is described in a later section of this booklet. Therefore, if you have a food allergy, it is extremely important for you to work with your healthcare professional to learn what foods cause your allergic reaction. NIAID I FOOD ALLERGY Sometimes, a reaction to food is not an allergy at all but another type of reaction called food intolerance. A description of food intolerance appears later in this booklet. 4 What Is an Allergic Reaction to Food? A food allergy occurs when the immune system responds to a harmless food as if it were a threat. The first time a person with food allergy is exposed to the food, no symptoms occur; but the first exposure primes the body to respond the next time. When the person eats the food again, an allergic response can occur. WHAT IS A FIRST EXPOSURE TO FOOD? Usually, the way you are first exposed to a food is when you eat it. But sometimes a first exposure or subsequent exposure can occur without your knowledge. This may be true in the case of peanut allergy. A person who experiences anaphylaxis on the first known exposure to peanut may have previously • Touched peanuts • Used a peanut-containing skin care product • Breathed in peanut dust in the home or when close to other people eating peanuts The Allergic Reaction Process Step 1: The first time you are exposed to a food allergen, your immune system reacts as if the food were harmful and makes specific IgE antibodies to that allergen. The antibodies circulate through your blood and attach to mast cells and basophils. Mast cells are found in all body tissues, especially in areas of your body that are typical sites of allergic reactions. Those sites include your nose, throat, lungs, skin, and gastrointestinal (GI) tract. Basophils are found in your blood and also in tissues that have become inflamed due to an allergic reaction. NIAID I FOOD ALLERGY An allergic reaction to food is a two-step process. 5 Step 2: The next time you are exposed to the same food allergen, it binds to the IgE antibodies that are attached to the mast cells and basophils. The binding signals the cells to release massive amounts of chemicals such as histamine. Depending on the tissue in which they are released, these chemicals will cause you to have various symptoms of food allergy. The symptoms can range from mild to severe. A severe allergic reaction can include a potentially life-threatening reaction called anaphylaxis. Generally, you are at greater risk for developing a food allergy if you come from a family in which allergies are common. These allergies are not necessarily food allergies but perhaps other allergic diseases, such as asthma or eczema (atopic dermatitis). If you have two parents who have allergies, you are more likely to develop food allergy than someone with one parent who has allergies. An allergic reaction to food usually takes place within a few minutes to several hours after exposure to the allergen. The process of eating and digesting food and the location of mast cells both affect the timing and location of the reaction. Symptoms of Food Allergy If you are allergic to a particular food, you may experience all or some of the following symptoms: • Itching in your mouth • Swelling of lips and tongue • GI symptoms, such as vomiting, diarrhea, or abdominal cramps and pain NIAID I FOOD ALLERGY • Hives 6 • Worsening of eczema • Tightening of the throat or trouble breathing • Drop in blood pressure EOSINOPHILIC ESOPHAGITIS Eosinophilic esophagitis (EoE) is a newly recognized chronic disease that can be associated with food allergies. It is increasingly being diagnosed in children and adults. Symptoms of EoE include nausea, vomiting, and abdominal pain after eating. A person may also have symptoms that resemble acid reflux from the stomach. In older children and adults, it can cause more severe symptoms, such as difficulty swallowing solid food or solid food sticking in the esophagus for more than a few minutes. In infants, this disease may be associated with failure to thrive. If you are diagnosed with EoE, you will probably be tested for allergies. In some situations, avoiding certain food allergens will be an effective treatment for EoE. CROSS-REACTIVE FOOD ALLERGIES NIAID I FOOD ALLERGY If you have a life-threatening reaction to a certain food, your healthcare professional will show you how to avoid similar foods that may trigger this reaction. For example, if you have a history of allergy to shrimp, allergy testing will usually show that you are also allergic to other shellfish, such as crab, lobster, and crayfish. This is called cross-reactivity. 7 What Is Anaphylaxis? If you have a food allergy, there is a chance that you may experience a severe form of allergic reaction known as anaphylaxis. Anaphylaxis may begin suddenly and may lead to death if not immediately treated. Anaphylaxis includes a wide range of symptoms that can occur in many combinations. Some symptoms are not life-threatening, but the most severe restrict breathing and blood circulation. Many different parts of your body can be affected. • Skin—itching, hives, redness, swelling • Nose—sneezing, stuffy nose, runny nose • Mouth—itching, swelling of lips or tongue • Throat—itching, tightness, difficulty swallowing, hoarseness • Chest—shortness of breath, cough, wheeze, chest pain, tightness • Heart—weak pulse, passing out, shock • GI tract—vomiting, diarrhea, cramps NIAID I FOOD ALLERGY • Nervous system—dizziness or fainting 8 Symptoms may begin within several minutes to several hours after exposure to the food. Sometimes the symptoms go away, only to return 2 to 4 hours later or even as many as 8 hours later. When you begin to experience symptoms, you must seek immediate medical attention because anaphylaxis can be lifethreatening. Anaphylaxis caused by an allergic reaction to a certain food is highly unpredictable. The severity of a given attack does not predict the severity of subsequent attacks. The response will vary depending on several factors, such as • Your sensitivity to the food • How much of the food you are exposed to • How the food entered your body Any anaphylactic reaction may become dangerous and must be evaluated by a healthcare professional. Food allergy is the leading cause of anaphylaxis. However, medications, insect stings, and latex can also cause an allergic reaction that leads to anaphylaxis. HOW DO YOU KNOW IF A PERSON IS HAVING AN ANAPHYLACTIC REACTION? Anaphylaxis is highly likely if at least one of the following three conditions occurs: 2. A person was exposed to an allergen likely to cause an allergic reaction, and, within minutes or several hours, two or more of the following symptoms occur: • Skin symptoms or swollen lips • Difficulty breathing • A drop in blood pressure • GI symptoms such as vomiting, diarrhea, or cramping 3. A person exposed to an allergen previously known to cause an allergic reaction in that person experiences a drop in blood pressure NIAID I FOOD ALLERGY 1. Within minutes or several hours of the onset of an illness, a person has skin symptoms (redness, itching, hives) or swollen lips and either • Difficulty breathing, or • A drop in blood pressure 9 Common Food Allergies in Infants, Children, and Adults In infants and children, the most common foods that cause allergic reactions are • Egg • Milk • Peanut • Tree nuts such as walnuts • Soy (primarily in infants) • Wheat In adults, the most common foods that cause allergic reactions are • Shellfi...
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