Abstract/Text: BACKGROUND: Egg allergy is very common, affecting 1% to 2% of children. It is generally thought that the majority of children with egg allergy develop tolerance in early childhood; however, this has not been examined in a large cohort with egg allergy.
OBJECTIVE: The purpose of the study was to estimate the proportion of children with egg allergy who develop egg tolerance and to identify predictors of tolerance development.
METHODS: Retrospective chart review of patients with egg allergy seen in a tertiary referral clinic. Patients were considered to have developed egg tolerance if they tolerated concentrated egg.
RESULTS: Kaplan-Meier analysis predicted resolution in 4% of patients with egg allergy by age 4 years, 12% by age 6 years, 37% by age 10 years, and 68% by age 16 years. Patients with persistent egg allergy had higher egg IgE levels at all ages to age 18 years. A patient's highest recorded egg IgE, presence of other atopic disease, and presence of other food allergy were significantly related to egg allergy persistence.
CONCLUSION: A majority of patients with egg allergy will develop egg tolerance, although the rate of tolerance development is slower than described previously. Egg IgE is predictive of allergy outcome and should be used in counseling patients on prognosis.
CLINICAL IMPLICATIONS: Most patients with egg allergy are likely to develop egg tolerance by late childhood, with the exception of patients with an egg IgE greater than 50 kU/L, who are unlikely to develop egg tolerance.

Abstract/Text: BACKGROUND: Cow's milk allergy (CMA) is the most common food allergy in infants and young children, affecting 2% to 3% of the general population. Most studies have shown the prognosis of developing tolerance to cow's milk to be good, with most outgrowing their allergy by age 3 years.
OBJECTIVE: To define the natural course of CMA and identify the factors that best predict outcome in a large referral population of children with CMA.
METHODS: Clinical history, test results, and final outcome were collected on 807 patients with IgE-mediated CMA. Patients were considered tolerant after they passed a challenge or experienced no reactions in the past 12 months and had a cow's milk IgE (cm-IgE) level <3 kU/L.
RESULTS: Rates of resolution were 19% by age 4 years, 42% by age 8 years, 64% by age 12 years, and 79% by 16 years. Patients with persistent allergy had higher cm-IgE levels at all ages to age 16 years. The highest cm-IgE for each patient, defined as peak cm-IgE, was found to be highly predictive of outcome (P < .001). Coexisting asthma (P < .001) and allergic rhinitis (P < .001) were also significant predictors of outcome.
CONCLUSION: The prognosis for CMA in this population is worse than previously reported. However, some patients developed tolerance during adolescence, indicating that follow-up and re-evaluation of CMA patients is important in their care. cm-IgE level is highly predictive of outcome.
CLINICAL IMPLICATIONS: The increasing potential for persistence of CMA, along with cm-IgE level's effect on prognosis, should be considered when counseling families regarding expected clinical course.

Abstract/Text: BACKGROUND: Wheat allergy is 1 of the most common food allergies in children, yet few data are available regarding its natural history.
OBJECTIVES: To define the natural course of wheat allergy and identify factors that help predict outcome in a large referral population of children with wheat allergy.
METHODS: Patients were included in the study if they had a history of a symptomatic reaction to wheat and a positive wheat IgE test result. Clinical history, laboratory results, and final outcome were recorded for 103 patients who met the inclusion criteria. Resolution of wheat allergy was determined based on food challenge results. Kaplan-Meier survival curves were generated to depict resolution of wheat allergy.
RESULTS: Rates of resolution were 29% by 4 years, 56% by 8 years, and 65% by 12 years. Higher wheat IgE levels were associated with poorer outcomes. The peak wheat IgE level recorded was a useful predictor of persistent allergy (P < .001), although many children outgrew wheat allergy with even the highest levels of wheat IgE.
CONCLUSION: The median age of resolution of wheat allergy is approximately 6 1/2 years in this population. In a significant minority of patients, wheat allergy persists into adolescence.

Abstract/Text: INTRODUCTION: There are limited reports on the natural history of hen's egg (HE) allergy (HEA) in children <6 years. We aimed to investigate the natural history of HEA in children aged 6-12 years and the factors affecting its tolerance acquisition.
METHODS: Using the database in our hospital, a total of 137 patients diagnosed with a definitive immediate-type reaction to HE when they turned 6 years were enrolled, and the natural course of HEA was prospectively examined until patients turned 12 years. Tolerance was defined as being able to pass an oral food challenge to consume a half or whole heated HE or consume heated HE freely without symptoms. Thirty patients (21.9%) who were enrolled for oral immunotherapy and 21 (15.3%) who discontinued follow-up were considered dropouts. Kaplan-Meier estimation was used to evaluate the rate of tolerance.
RESULTS: Fifty-five of the 137 patients (40.1%) had a previous HE anaphylaxis history; 61 (44.5%) patients had acquired tolerance to HE by age 12 years; and 25 (18.2%) continued total or partial HE elimination. The estimated acquired tolerance rates by ages 7, 9, and 12 years were 14.6%, 40.8%, and 60.5%, respectively. A previous history of HE anaphylaxis before 6 years of age, reacting to small amounts of heated HE by 6 years of age, and higher ovomucoid-specific immunoglobulin E values at the same age were associated with persistent HEA.
CONCLUSION: This study provides important insights into the natural course of HEA beyond early childhood, with the acquisition of HE tolerance continuing throughout the duration of the study.

© 2021 S. Karger AG, Basel.

Abstract/Text: BACKGROUND: Hen's egg (HE) allergy develops during infancy. We investigated tolerance acquisition in Japanese children allergic to HE aging <6 years.
METHODS: In this retrospective study, 226 children born in 2005 with a history of immediate-type HE allergy underwent an oral food challenge (OFC). Tolerance was defined as no reaction to an OFC with half of whole heated HE or accidental HE consumption at home. Participants were divided into three groups based on age at tolerance acquisition: group I (<3 years) (n = 66), group II (3-6 years) (n = 98), and group III (prolonged allergic groups) (n = 62).
RESULTS: Tolerance acquisition occurred in 30% (66/226) by 3 years of age, 59% (133/226) by 5 years of age, and 73% (164/226) at 6 years of age. At 3 years, incidences of allergy-related complications (bronchial asthma, p = 0.02; atopic dermatitis, p = 0.04) were higher in the group III than in the group I. Anaphylaxis to any food occurred more frequently in the group III than in the group I (p = 0.03); anaphylaxis to HE was more common in the group III (p = 0.04). Egg white (EW)- and ovomucoid (OM)-specific immunoglobulin E (IgE) levels were higher in the group III than in the group I (p < 0.05).
CONCLUSIONS: The group III experienced HE-related anaphylaxis and complications more frequently and exhibited sustained, high EW- and OM-specific IgE levels.

Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Abstract/Text: BACKGROUND: Wheat allergy is the third most common food allergy that develops during infancy in Japan. To identify factors associated with persistent wheat allergy, we assessed the rate of tolerance acquisition among Japanese children aged less than 6 years with an immediate-type wheat allergy using the oral food challenge (OFC) method.
METHODS: This retrospective cohort study included 83 children (born in 2005-2006) who had a history of immediate-type allergic reaction to wheat and were followed until 6 years of age. The subjects were divided to form "tolerant" (n = 55; tolerance acquired by 6 years of age) and "allergic" (n = 28; tolerance not acquired by 6 years of age) groups based on their OFC results.
RESULTS: The rates of tolerance acquisition to 200 g of udon noodles at 3, 5, and 6 years of age were 20.5% (17/83), 54.2% (45/83), and 66.3% (55/83), respectively. The total number of anaphylactic reactions experienced prior to 3 years of age in response to all foods (p < 0.01) and to wheat (p = 0.043) was significantly higher in the allergic than in the tolerant group. Wheat- and ω-5 gliadin-specific immunoglobulin E (IgE) levels were significantly higher in the allergic group than in the tolerant group (p < 0.01), and wheat-specific IgE levels were more likely to increase after infancy in the allergic group.
CONCLUSIONS: A history of anaphylaxis to all foods including wheat and/or a high level of wheat- or ω-5 gliadin-specific IgE antibodies were identified as risk factors for persistent wheat allergy.

© 2018 S. Karger AG, Basel.

Abstract/Text: BACKGROUND: Cow's milk (CM) allergy is the second most common food allergy developed during infancy in Japan. To identify predictors of persistent CM allergy, we investigated the tolerance acquisition rate based on an oral food challenge in children under 6 years of age, diagnosed with immediate-type CM allergy.
METHODS: This retrospective cohort study included 131 children born in 2005 with a history of immediate allergic reaction to CM, of whom 39 were excluded because of ongoing oral immunotherapy (n = 18) or a lack of follow-up data (n = 21). The 92 remaining participants were followed for 6 years. Tolerance was defined as no adverse reaction to 200 mL of CM and regular intake of milk at home. Subjects were divided into 3 groups based on age at tolerance acquisition: group I (<3 years; n = 31), group II (3-6 years; n = 42), and group III (persistent allergic group; n = 19).
RESULTS: Tolerance acquisition rates by 3, 5, and 6 years of age were 32.6% (30/92), 64.1% (59/92), and 84.8% (70/92), respectively. Age at first hospital visit was significantly higher in groups II and III than in group I (p < 0.001). The incidence of anaphylaxis to other foods was also higher in group III than in group I (p = 0.04), as was CM-induced anaphylaxis (p = 0.03). Furthermore, milk and casein-specific immunoglobulin E (IgE) levels were significantly higher in group III than in group II after birth and remained high thereafter (p < 0.05).
CONCLUSIONS: The history of anaphylaxis and high milk-specific IgE levels were associated with persistent CM allergy.

© 2018 S. Karger AG, Basel.

Abstract/Text: BACKGROUND: Some breastfed infants with atopic eczema benefit from elimination of cow milk, egg, or other antigens from their mother's diet. Maternal dietary antigens are also known to cross the placenta.
OBJECTIVES: To assess the effects of prescribing an antigen avoidance diet during pregnancy or lactation, or both, on maternal and infant nutrition and on the prevention or treatment of atopic disease in the child.
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 July 2012).
SELECTION CRITERIA: All randomized or quasi-randomized comparisons of maternal dietary antigen avoidance prescribed to pregnant or lactating women. We excluded trials of multimodal interventions that included manipulation of the infant's diet other than breast milk or of non-dietary aspects of the infant's environment.
DATA COLLECTION AND ANALYSIS: We extracted data from published reports, supplemented by additional information received from the trialists we contacted.
MAIN RESULTS: The evidence from five trials, involving 952 participants, does not suggest a protective effect of maternal dietary antigen avoidance during pregnancy on the incidence of atopic eczema during the first 18 months of life. Data on allergic rhinitis or conjunctivitis, or both, and urticaria are limited to a single trial each and are insufficient to draw meaningful inferences. Longer-term atopic outcomes have not been reported. The restricted diet during pregnancy was associated with a slightly but statistically significantly lower mean gestational weight gain, a non-significantly higher risk of preterm birth, and a non-significant reduction in mean birthweight.The evidence from two trials, involving 523 participants, did not observe a significant protective effect of maternal antigen avoidance during lactation on the incidence of atopic eczema during the first 18 months or on positive skin-prick tests to cow milk, egg, or peanut antigen at one, two, or seven years.One crossover trial involving 17 lactating mothers of infants with established atopic eczema found that maternal dietary antigen avoidance was associated with a non-significant reduction in eczema severity.
AUTHORS' CONCLUSIONS: Prescription of an antigen avoidance diet to a high-risk woman during pregnancy is unlikely to reduce substantially her child's risk of atopic diseases, and such a diet may adversely affect maternal or fetal nutrition, or both. Prescription of an antigen avoidance diet to a high-risk woman during lactation may reduce her child's risk of developing atopic eczema, but better trials are needed.Dietary antigen avoidance by lactating mothers of infants with atopic eczema may reduce the severity of the eczema, but larger trials are needed.

Abstract/Text: BACKGROUND: The mainstay of treatment of IgE-mediated cow milk allergy (IMCMA) is an avoidance diet, which is especially difficult with a ubiquitous food like milk. Milk oral immunotherapy (MOIT) may be an alternative treatment, through desensitization or induction of tolerance.
OBJECTIVES: We aim to assess the clinical efficacy and safety of MOIT in children and adults with IMCMA as compared to a placebo treatment or avoidance strategy.
SEARCH METHODS: We searched 13 databases for journal articles, conference proceedings, theses and unpublished trials, without language or date restrictions, using a combination of subject headings and text words. The search is up-to-date as of October 1, 2012.
SELECTION CRITERIA: Only randomised controlled trials (RCT) were considered for inclusion. Blinded and open trial designs were included. Children and adults with IMCMA were included. MOIT administered by any protocol were included.
DATA COLLECTION AND ANALYSIS: A total of 2111 unique records were identified and screened for potential inclusion. Studies were selected, data extracted and methodological quality assessed independently by two reviewers. We attempted to contact the study investigators to inquire about data not published that was required for the analysis. Statistical heterogeneity was assessed using the I² test. We estimated a pooled risk ratio (RR) for each outcome using a Mantel-Haenzel fixed-effect model if statistical heterogeneity was low as evaluated by an I² value less than 50%.
MAIN RESULTS: Of 157 records reviewed, 16 were included, representing five trials. In general, the studies were small and had inconsistent methodological rigor. Overall, the quality of evidence was rated as low. Each study used a different MOIT protocol. A total of 196 patients were studied (106 MOIT, 90 control) and all were children. Three studies were blinded and two used an avoidance diet control.  Sixty-six patients (62%) in the MOIT group were able to tolerate a full serving of milk (about 200 mL) compared to seven (8%) of the control group (RR 6.61, 95% CI 3.51 to 12.44). In addition, 27 (25%) in the MOIT group could ingest a partial serving of milk (10 to 184 mL) while none could in the control group (RR 9.34, 95% CI 2.72 to 32.09). None of the studies assessed the patients following a period off immunotherapy. Adverse reactions were common (97 of 106 MOIT patients had at least one symptom), although most were local and mild. Because of variability in reporting methods, adverse effects could not be combined quantitatively. For every 11 patients receiving MOIT, one required intramuscular epinephrine. One patient required it on two occasions.
AUTHORS' CONCLUSIONS: Studies to date have involved small numbers of patients and the quality of evidence is generally low. The current evidence shows that MOIT can lead to desensitization in the majority of individuals with IMCMA although the development of long-term tolerance has not been established. A major drawback of MOIT is the frequency of adverse effects, although most are mild and self-limited. The use of parenteral epinephrine is not infrequent. Because there are no standardized protocols, guidelines would be required prior to incorporating desensitization into clinical practice.

Abstract/Text: BACKGROUND: The age at which allergenic foods should be introduced into the diet of breast-fed infants is uncertain. We evaluated whether the early introduction of allergenic foods in the diet of breast-fed infants would protect against the development of food allergy.
METHODS: We recruited, from the general population, 1303 exclusively breast-fed infants who were 3 months of age and randomly assigned them to the early introduction of six allergenic foods (peanut, cooked egg, cow's milk, sesame, whitefish, and wheat; early-introduction group) or to the current practice recommended in the United Kingdom of exclusive breast-feeding to approximately 6 months of age (standard-introduction group). The primary outcome was food allergy to one or more of the six foods between 1 year and 3 years of age.
RESULTS: In the intention-to-treat analysis, food allergy to one or more of the six intervention foods developed in 7.1% of the participants in the standard-introduction group (42 of 595 participants) and in 5.6% of those in the early-introduction group (32 of 567) (P=0.32). In the per-protocol analysis, the prevalence of any food allergy was significantly lower in the early-introduction group than in the standard-introduction group (2.4% vs. 7.3%, P=0.01), as was the prevalence of peanut allergy (0% vs. 2.5%, P=0.003) and egg allergy (1.4% vs. 5.5%, P=0.009); there were no significant effects with respect to milk, sesame, fish, or wheat. The consumption of 2 g per week of peanut or egg-white protein was associated with a significantly lower prevalence of these respective allergies than was less consumption. The early introduction of all six foods was not easily achieved but was safe.
CONCLUSIONS: The trial did not show the efficacy of early introduction of allergenic foods in an intention-to-treat analysis. Further analysis raised the question of whether the prevention of food allergy by means of early introduction of multiple allergenic foods was dose-dependent. (Funded by the Food Standards Agency and others; EAT Current Controlled Trials number, ISRCTN14254740.).

Abstract/Text: BACKGROUND: The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut consumption and avoidance to determine which strategy is most effective in preventing the development of peanut allergy in infants at high risk for the allergy.
METHODS: We randomly assigned 640 infants with severe eczema, egg allergy, or both to consume or avoid peanuts until 60 months of age. Participants, who were at least 4 months but younger than 11 months of age at randomization, were assigned to separate study cohorts on the basis of preexisting sensitivity to peanut extract, which was determined with the use of a skin-prick test--one consisting of participants with no measurable wheal after testing and the other consisting of those with a wheal measuring 1 to 4 mm in diameter. The primary outcome, which was assessed independently in each cohort, was the proportion of participants with peanut allergy at 60 months of age.
RESULTS: Among the 530 infants in the intention-to-treat population who initially had negative results on the skin-prick test, the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group and 1.9% in the consumption group (P<0.001). Among the 98 participants in the intention-to-treat population who initially had positive test results, the prevalence of peanut allergy was 35.3% in the avoidance group and 10.6% in the consumption group (P=0.004). There was no significant between-group difference in the incidence of serious adverse events. Increases in levels of peanut-specific IgG4 antibody occurred predominantly in the consumption group; a greater percentage of participants in the avoidance group had elevated titers of peanut-specific IgE antibody. A larger wheal on the skin-prick test and a lower ratio of peanut-specific IgG4:IgE were associated with peanut allergy.
CONCLUSIONS: The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00329784.).

Abstract/Text: BACKGROUND: In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group).
METHODS: At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age.
RESULTS: We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], P<0.001). Three new cases of allergy developed in each group, but after 12 months of avoidance there was no significant increase in the prevalence of allergy among participants in the consumption group (3.6% [10 of 274 participants] at 60 months and 4.8% [13 of 270] at 72 months, P=0.25). Fewer participants in the peanut-consumption group than in the peanut-avoidance group had high levels of Ara h2 (a component of peanut protein)-specific IgE and peanut-specific IgE; in addition, participants in the peanut-consumption group continued to have a higher level of peanut-specific IgG4 and a higher peanut-specific IgG4:IgE ratio.
CONCLUSIONS: Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known. (Funded by the National Institute of Allergy and Infectious Diseases and others; LEAP-On ClinicalTrials.gov number, NCT01366846.).

Abstract/Text: BACKGROUND: Evidence is accumulating that early consumption is more beneficial than is delayed introduction as a strategy for primary prevention of food allergy. However, allergic reactions caused by early introduction of such solid foods have been a problematic issue. We investigated whether or not early stepwise introduction of eggs to infants with eczema combined with optimal eczema treatment would prevent egg allergy at 1 year of age.
METHODS: In this randomised, double-blind, placebo-controlled trial, we enrolled infants 4-5 months of age with eczema from two centres in Japan. Exclusion criteria were being born before 37 weeks of gestational age, experience of ingestion of hen's eggs or egg products, history of immediate allergic reaction to hen's eggs, history of non-immediate allergic reaction to a particular type of food, and complications of any severe disease. Infants were randomly assigned (block size of four; stratified by institution and sex) to early introduction of egg or placebo (1:1). Participants in the egg group consumed orally 50 mg of heated egg powder per day from 6 months to 9 months of age and 250 mg per day thereafter until 12 months of age. We aggressively treated participants' eczema at entry and maintained control without exacerbations throughout the intervention period. Participants and physicians were masked to assignment, and allocation was concealed. The primary outcome was the proportion of participants with hen's egg allergy confirmed by open oral food challenges at 12 months of age, assessed blindly by standardised methods, in all randomly allocated participants who received the intervention. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000008673.
FINDINGS: Between Sept 18, 2012, and Feb 13, 2015, we randomly allocated 147 participants (73 [50%] to the egg group and 74 [50%] to the placebo group). This trial was terminated on the basis of the results of the scheduled interim analysis of 100 participants, which showed a significant difference between the two groups (four [9%] of 47 participants had an egg allergy in the egg group vs 18 [38%] of 47 in the placebo group; risk ratio 0·222 [95% CI 0·081-0·607]; p=0·0012). In the primary analysis population, five (8%) of 60 participants had an egg allergy in the egg group compared with 23 (38%) of 61 in the placebo group (risk ratio 0·221 [0·090-0·543]; p=0·0001). The only difference in adverse events between groups was admissions to hospital (six [10%] of 60 in the egg group vs none in the placebo group; p=0·022). 19 acute events occurred in nine (15%) participants in the egg group versus 14 events in 11 (18%) participants in the placebo group after intake of the trial powder.
INTERPRETATION: Introduction of heated egg in a stepwise manner along with aggressive eczema treatment is a safe and efficacious way to prevent hen's egg allergy in high-risk infants. In this study, we developed a practical approach to overcome the second wave of the allergic epidemic caused by food allergy.
FUNDING: Ministry of Health, Labour and Welfare, and National Centre for Child Health and Development, Japan.

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