Oral Food Challenge Research Articles

Importance of oral food challenge and identification of atopic dermatitis in child with Netherton syndrome: A case report

Importance of oral food challenge and identification of atopic dermatitis in child with Netherton syndrome: A case report

Alternative Fish Species for Nutritional Management of Children with Fish-FPIES-A Clinical Approach.

In the Mediterranean region, fish is a common cause of food protein-induced enterocolitis syndrome (FPIES) in children. No laboratory tests specific to FPIES are available, and oral food challenge (OFC) is the gold standard for its diagnosis and testing for achievement of tolerance. Children with FPIES to fish are usually advised to avoid all fish, regardless of the species. Fish are typically classified into bony and cartilaginous, which are phylogenetically distant species and therefore contain less cross-reacting allergens. The protein β-parvalbumin, considered a pan-allergenic, is found in bony fish, while the non-allergenic α-parvalbumin is commonly found in cartilaginous fish. Based on this difference, as a first step in the therapeutic process of children with FPIES caused by a certain fish in the bony fish category (i.e., hake, cod, perch, sardine, gilthead sea bream, red mullet, sole, megrim, sea bass, anchovy, tuna, swordfish, trout, etc.), an OFC to an alternative from the category of cartilaginous fish is suggested (i.e., blue shark, tope shark, dogfish, monkfish, skate, and ray) and vice versa. Regarding the increased mercury content in some sharks and other large species, the maximum limit imposed by the European Food Safety Authority (EFSA) for weekly mercury intake must be considered. An algorithm for the management of fish-FPIES, including alternative fish species, is proposed.

CQ3 日本のIgE依存性鶏卵アレルギー患者もしくはその疑いのある者において，食物経口負荷試験は完全除去回避に有用か？

CQ3 日本のIgE依存性鶏卵アレルギー患者もしくはその疑いのある者において，食物経口負荷試験は完全除去回避に有用か？

鶏卵食物アレルギーの診断を目的に卵白特異的IgE抗体価により総負荷量を設定した食物経口負荷試験の検討：症例集積研究

鶏卵食物アレルギーの診断を目的に卵白特異的IgE抗体価により総負荷量を設定した食物経口負荷試験の検討：症例集積研究

Is oral food challenge test useful for avoiding complete elimination of cow's milk in Japanese patients with or suspected of having IgE-dependent cow's milk allergy?

Is oral food challenge test useful for avoiding complete elimination of cow's milk in Japanese patients with or suspected of having IgE-dependent cow's milk allergy?

Threshold of Reactivity and Tolerance to Precautionary Allergen-Labelled Biscuits of Baked Milk- and Egg-Allergic Children

Extremely sensitive food-allergic patients may react to very small amounts of allergenic foods. Precautionary allergen labelling (PAL) warns from possible allergenic contaminations. We evaluated by oral food challenge the reactivity to a brand of PAL-labelled milk- and egg-free biscuits of children with severe milk and egg allergy. We explored the ability of proteomic methods to identify minute amounts of milk/egg allergens in such biscuits. Traces of milk and/or egg allergens in biscuits were measured by two different liquid-chromatography-mass spectrometry methods. The binding of patient’s serum with egg/milk proteins was assessed using immunoblotting. None of the patients reacted to biscuits. Egg and milk proteins were undetectable with a limit of detection of 0.6 µg/g for milk and egg (method A), and of 0.1 and 0.3 µg /g for milk and egg, respectively (method B). The immunoblots did not show milk/egg proteins in the studied biscuits. Milk/egg content of the biscuits is far lower than 4 µg of milk or egg protein per gram of product, the minimal doses considered theoretically capable of causing reactions. With high sensitivity, proteomic assessments predict the harmlessness of very small amount of allergens in foods, and can be used to help avoiding unnecessary PAL.

Milk and cow’s meat allergy in a child: A clinical case

Allergy to bovine serum albumin is the main predictor of beef allergy associated with cow’s milk proteins allergy. We report a case of a 3-year-old child with cow’s milk proteins allergy since the age of 6 months who, after some ingestions of beef, developed episodes of irritability, urticaria and syncope. Specific IgE to beef, oral food challenge with medium rare cooked beef and specific IgE to bovine serum albumin were all positive, but an oral food challenge with well cooked beef was tolerated. Allergy to bovine serum albumin is not usually associated with severe reactions, since it is a thermolabile protein, however, the process of cooking meat may be insufficient to have an effect on the complex matrix of meat and associated serum albumins. The irregular pattern of the episodes and the previous diagnosis of cow’s milk proteins allergy may act as confounding factors leading to a delayed diagnosis.

A 60-minute dosing interval is safer than a 30- or 40-minute interval in oral food challenge

BackgroundThe interval between antigen ingestion may influence the safety of oral food challenge tests (OFCs), especially in patients with severe food allergies. MethodsThis retrospective chart review of OFCs eliciting objective reactions to wheat, egg, and milk that were performed between April 2012 and January 2021 evaluated an equivalent number of low-dose OFCs performed at 30-, 40-, or 60-min intervals. To avoid the influence of the potential allergy severity of the patients, the prediction scores of all intervals were matched. We evaluated the total symptom score (TS), total ingested dose, and the proportions of severe reactions (TS ≥ 30) and adrenaline use. ResultsWe analyzed 945 OFCs (wheat, n = 186; egg, n = 561; milk, n = 198). The 60-min OFC had significantly lower TS than the 30- and 40-min OFC methods in wheat (p < 0.001 and p = 0.003, respectively), egg (p < 0.001 for both), and milk (p < 0.001 and p = 0.018, respectively). The total dose in the 60-min method was significantly lower than in the 30-min method (p < 0.001 for all). The proportion of severe reaction (TS ≥ 30) in the 60-min method was significantly lower than that in the 30-min method for the egg and milk OFCs (p = 0.001 and p < 0.001, respectively). There was no difference in the rates of adrenaline injection. ConclusionsThe 60-min interval is safer than 30- or 40-min intervals in wheat, egg, and milk OFCs in patients with a low threshold dose for food allergy.

Ana o 3 sIgE testing increases the accuracy of cashew allergy diagnosis using a two-step model.

Measurement of cashew-specific IgE (sIgE) is often used to confirm sensitization but does not reliably diagnose clinical allergy. Ana o 3 is the dominant cashew allergen detected in 75-100% of patients with cashew allergy but not currently used in clinical practice. To determine if component-resolved diagnostics using specific IgE to the 2 S albumin from cashew, Ana o 3, improves the accuracy of diagnosing cashew allergy, thereby circumventing the need for an oral food challenge (OFC) in some patients. A population-based sample of 5276 children was recruited at age 1year and followed up at age 6 years. Children with positive cashew skin prick test at age 6 underwent an OFC to clarify allergy status. Forty-seven children (mean age 5.02±0.2) (33 cashew-allergic and 14 cashew-tolerant) had cashew sIgE and Ana o 3 sIgE quantified by ImmunoCAP System FEIA. A cutoff of >0.32kUA/L for Ana o 3 sIgE provided 95% specificity and 90% sensitivity and correctly identified 90% of clinical cashew allergy. At the same specificity, the sensitivity for cashew sIgE (>8.5kUA/L) was only 26%. Sequential measurement of cashew sIgE followed by Ana o 3 sIgE diagnosed 90% of children with cashew allergy without the need for an OFC. Ana o 3 sIgE testing provides higher diagnostic accuracy than cashew sIgE. Sequential measurement of cashew sIgE followed by Ana o 3 removed the need for a food challenge from 66% down to 12.8% (5-fold) of children compared with cashew sIgE testing alone.

First Real-World Effectiveness Analysis of Preschool Peanut Oral Immunotherapy

To examine the effectiveness and safety of peanut oral immunotherapy (POIT) after 1 year of maintenance in preschool-aged children.In the study, researchers included 161 patients aged 9 to 70 months who successfully completed 1 year of maintenance POIT and were eligible for follow-up oral food challenge (OFC). The inclusion criteria were having a history of objective reaction to peanut and a positive test result (either a skin-prick test [SPT] or peanut-specific immunoglobulin E [ps-IgE]) or at least 1 objective reaction with dosing during build-up, along with a predetermined ps-IgE level and SPT wheal size.Preschoolers enrolled in the study were given gradually increasing peanut protein doses over 16–22 weeks at clinic visits, building up to a maintenance dose of 300 mg. The children then ingested 300 mg of peanut protein daily for a year. After ∼12 months, the participants were invited to participate in a follow-up peanut OFC. SPT and/or ps-IgE were obtained at baseline and selectively throughout the maintenance and follow-up OFC visits. Symptoms of allergic reactions occurring were recorded and graded 1 to 5.Of the patients who received a year of maintenance therapy and underwent follow-up OFC (n = 117), 92 (78.6%) tolerated a cumulative dose of 4000 mg peanut protein without any symptoms, and 115 (98.3%) tolerated at least 1000 mg. The dose tolerated had increased on average by 3969 mg in those with a negative follow-up OFC and by 3376 mg in those with a positive follow-up OFC. SPT wheal size was also significantly decreased after a year regardless of follow-up OFC result; however, the decrease in ps-IgE was not statistically significant. Those with reactions at the follow-up OFC had either grade 1 (14.5% of all who underwent OFC), grade 2 (6%), or grade 3 (0.85%). No one had a grade 4 or 5 reaction. Of the 124 patients with safety outcomes analyzed during maintenance therapy, 111 (89.5%) were symptom-free during POIT dosing, 10 (8.1%) had grade 1 reactions, 3 (2.4%) had grade 2 reactions, and only 2 (1.6%) required epinephrine for POIT dosing reactions.POIT is effective for preschoolers, protecting against at least 1000 mg peanut protein exposure after one year of maintenance therapy in 98.3% of children and allowing consumption of up to 4000 mg in 78.6%. It is also safe during maintenance, with nearly 90% of children symptom-free during maintenance dosing.POIT has emerged as a patient-preference–sensitive option to increase tolerance to peanut protein and protect against accidental exposure. Previous studies have revealed that increasing the peanut threshold to 1000 mg provides 99% protection from accidental exposures, and commercial POIT product is now approved in children 4 to 17 years old. This is the first real-world study revealing that the majority of preschoolers (98.3%) are able to tolerate 1000 mg after a year of POIT maintenance therapy. Mounting evidence suggests POIT may be safer and more effective when initiated at younger ages, likely because of a milder allergic phenotype, less patient aversion, and opportunity for better adherence from close parental supervision. Preschool POIT is a promising disease-modifying intervention that, in the context of shared decision-making with an experienced pediatric allergist, is likely to dramatically improve health and economic outcomes for patients and families.

White paper peanut allergy—part 2: Diagnosis of peanut allergy with special emphasis on molecular component diagnostics

Summary Background Peanut allergy is an immunoglobulin E (IgE)-mediated immune response that usually manifests in childhood and can range from mild skin reactions to anaphylaxis. Since quality of life maybe greatly reduced by the diagnosis of peanut allergy, an accurate diagnosis should always be made. Methods A selective literature search was performed in PubMed and consensus diagnostic algorithms are presented. Results Important diagnostic elements include a detailed clinical history, detection of peanut-specific sensitization by skin prick testing and/or in vitro measurement of peanut (extract)-specific IgE and/or molecular components, and double-blind, placebo-controlled food challenge as the gold standard. Using these tools, including published cut-off values, diagnostic algorithms were established for the following constellations: 1) Suspicion of primary peanut allergy with a history of immediate systemic reaction, 2) Suspicion of primary peanut allergy with questionable symptoms, 3) Incidental findings on sensitization testing and peanut ingestion so far or 4) Suspicion of pollen-associated peanut allergy with solely oropharyngeal symptoms. Conclusion The most important diagnostic measures in determining the diagnosis of peanut allergy are clinical history and detection of sensitizations, also via component-based diagnostics. However, in case of unclear results, the gold standard—an oral food challenge—should always be used.

Randomized Trial of Early Infant Formula Introduction to Prevent Cow’s Milk Allergy

To determine if the early introduction of cow’s milk formula (CMF) could prevent the development of cow’s milk allergy (CMA) in healthy infants.In the study, the researchers enrolled 491 newborns within 5 days of birth from 4 hospitals in Okinawa, Japan. Inclusion criteria were a gestational age of at least 35 weeks, a birth weight of at least 2000 g, and the absence of severe underlying disease.Participants were allowed to supplement with CMF before 1 month of age and underwent a screening oral food challenge (OFC) at that time. Those with a negative OFC result were randomly assigned to either the open-label CMF ingestion or avoidance. Those in the CMF ingestion group ingested at least 10 mL of CMF daily between 1 and 2 months of age, whereas those in the avoidance group were instructed to supplement with soy formula if needed during this time. At 3 months of age, an open OFC was performed on all participants. Those who were negative from both groups spontaneously ingested CMF to supplement breastfeeding until 6 months of age, at which time a second open OFC was performed on all participants.The modified intention-to-treat analysis revealed a significantly lower rate of CMA in the ingestion group versus the avoidance group at 6 months of age (0.8% vs 6.8%; respectively; P < .001). Approximately 70% were still breastfed, and no mothers had eliminated cow’s milk. There were no differences in the rate of eczema or sensitization to egg, wheat, or soy between groups.Daily ingestion of at least 10 mL of CMF between 1 and 2 months of life decreased the rate of OFC-confirmed CMA in infants. The early introduction of CMF did not impede breastfeeding.Data supporting the benefit of early introduction of allergenic foods in preventing allergy are accumulating. In this study, researchers examined the impact of introducing a specific daily minimum quantity of CMF in the general infant population, with favorable results. In further studies, researchers could provide interventions in a blinded manner and/or examine the impact of CMF introduction in infants at high-risk of allergy.

Rectal Bleeding and Cow’s Milk Protein-induced Allergic Proctocolitis: A Prospective Study

To assess time to resolution of food protein–induced allergic proctocolitis (FPIAP).In this study, researchers evaluated 76 infants aged <4 months with rectal bleeding (RB) referred to the pediatric gastrointestinal department at Trousseau Hospital in Paris, France, between May 2014 and December 2017. Only infants whose RB responded to a cow’s milk elimination diet were included in the study.This was a prospective cohort of infants with concern for cow’s milk protein (CMP) allergy who had resolution of RB with CMP elimination. Exclusion criteria included RB because of another etiology and exclusively breastfed infants. A total of 2 to 8 weeks after resolution of RB, CMP oral food challenge (OFC) was completed. If FPIAP was confirmed, OFC was repeated every 2 months after the age of 4 months to assess the time to tolerance of CMP. Ongoing FPIAP CMP was defined as RB, behavioral change, diarrhea, and vomiting. Tolerance was defined as CMP daily without symptoms.Only 31% of the cohort failed OFC at initial diagnostic challenge, meaning that over two-thirds of infants who initially responded to CMP exclusion did not have return of symptoms on rechallenge just weeks later. Of the patients confirmed to have FPIAP CMP, the median age of tolerance was determined to be 6.8 months, with >75% of the cohort tolerant by 10 months. Infants with a first-degree family history of atopic disease developed tolerance later (8.9 months versus 5.1 months).In this work, it was confirmed that the majority of RB in infants is likely not related to FPIAP CMP. This study also revealed that the time to resolution might be earlier than previously thought.Although there are no solid guidelines on introduction of CMP in presumed FPIAP CMP, the majority of patients exclude CMP until approximately 1 year. In this study, it was found that only one-third of RB before 4 months was due to FPIAP. Of those with FPIAP, CMP could be challenged earlier and at more frequent intervals depending on family wishes. A major limitation of this study is that exclusively breastfed infants were excluded and the lack of information on maternal diet in those who were nursing.

Increased IgE-Mediated Food Allergy With Food Protein-Induced Allergic Proctocolitis

To examine the relationship between food protein-induced allergic proctocolitis (FPIAP) and the risk of developing immunoglobulin E–mediated food allergy (IgE-FA) in infants.In the study, the researchers included 903 infants who were enrolled in the Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) cohort, an observational healthy-infant cohort study in which researchers characterized the epidemiology of FPIAP in the primary care setting.Infants diagnosed with FPIAP with presence of documented blood in the stool were included. IgE-FA was determined by 2 allergists independently reviewing clinical and sensitization data from children whose parents reported suspect reactions and included if both reviewers agreed the diagnosis was “confirmed” or probable.” The rate of IgE-FA was compared between healthy infants and those with FPIAP. Additional variables, including the presence of eczema, were evaluated by using univariable and multivariable logistic regression.More children with FPIAP developed IgE-FA (11%), compared with healthy children (5%). Adjusting for eczema, children with FPIAP had twice the odds of developing IgE-FA to any food. FPIAP was most strongly associated with IgE-FA to milk, although the study was not powered to detect relationships to individual foods.Children with FPIAP were at an increased risk for having IgE-FA. This may be multifactorial, including shared pathogenesis in the development of FPIAP and IgE-FA and/or an effect of antigen elimination diet used to treat FPIAP.FPIAP is a common diagnosis early in infancy that is benign and self-resolved. However, a diagnosis of FPIAP often leads to prolonged dietary restriction from cow’s milk (the most common cause) and potentially soy protein as well. Although conventional teaching is to wait until 12 months of age to reintroduce dairy to infants with FPIAP, it can likely be introduced much earlier. In this study, researchers found an association between a diagnosis of FPIAP with increased risk for IgE-FA, although diagnosis was not confirmed through oral food challenges. Although the authors report some potential common immunologic pathways between FPIAP (a non–immunoglobulin E–mediated food reaction) and IgE-FA, a true causative effect has not been established. Now that current evidence-based guidelines recommend early introduction of allergenic foods to all infants (beginning ∼4-6 months of age) and ongoing inclusion in the diet as the best path toward food allergy prevention, with this study, the authors reinforce the need for pediatricians to discuss these guidelines with parents. This is especially true in infants at a higher risk to develop food allergy, including those with severe or persistent atopic dermatitis and now, potentially, other forms of non–immunoglobulin–mediated food allergy. Now, more than ever, we need to let the infants eat!

Deserters on the Atopic March: Risk Factors, Immune Profile and Clinical Outcomes of Food Sensitized-Tolerant Infants

To investigate the phenotypic features of infants who demonstrate immunoglobulin E sensitization to foods that they clinically tolerate. Such understanding may help elucidate strategies in the prevention of food allergies.A birth cohort of 1074 from southeastern Australia was composed of subjects <32 weeks’ gestation at time of enrollment and the mother planning to give birth at a local hospital. Participants were characterized as nonsensitized, sensitized-tolerant (ST), or food allergic (FA) on the basis of skin-prick testing and food challenge at 12 month of age.Environmental exposures were recorded throughout the study period of the cohort. Cord blood regulatory T-cell populations were measured at birth. Subsequent childhood allergic disease was assessed by parent report, clinical examination, and repeat skin-prick testing.Covariants were assessed among nonsensitized (n = 698), ST (n = 27), and FA (n = 61) groups and revealed that the ST group was more similar to the nonsensitized group than to the FA group in the following measures: family history of eczema (nonsensitized: 44.6%; ST: 44.6%; FA: 65.6%), pet ownership at 12 months (nonsensitized: 71.5%; ST: 81.5%; FA: 45.8%), eczema during the first 12 months (nonsensitized: 19%; ST: 32%; FA: 64%), and aeroallergen sensitivity at the age of 4 years (nonsensitized: 19.1%; ST 28.6%; FA 44.4%). At birth, a higher proportion of activated regulatory T cells was associated with the ST group.Infants who are sensitized but tolerant have similar pattern of exposures, immunity, and outcomes to nonsensitized infants. An elevated proportion of activated regulatory T cells at birth was specific to the ST infants and may be relevant to the clinical suppression of disease.Genetic and environmental factors are well known to play a role in the development of allergies. With this study, the authors compare prebirth cohorts to determine more specific factors that may put infants at higher risk for developing food allergies. A robust method of skin-prick testing plus an oral food challenge was used to confirm food allergies. The differences in proportion of cord blood naïve versus activated regulatory T cells in cohort groups provides insight into a mechanism for the prevention of food allergies.

Single-Dose Oral Challenges to Validate Eliciting Doses in Children With Cow’s Milk Allergy

To validate the predicted ED05 for cow’s milk, which is the allergen dose that elicits an objective reaction in 5% of a population, of 0.5 mg of cow’s milk protein (0.015 mL of fresh cow’s milk).The study included 182 children between the ages of 6 months and 17 years recruited from 4 centers in the United Kingdom, Ireland, and Spain. Inclusion criteria varied across centers. Participants had to have cow’s milk allergy (CMA), defined by either a clinical history and immunoglobulin E (IgE) sensitization and/or positive food challenge result.The participants were given 0.5 mg of milk protein as either a single unblinded administration or the first dose of a double-blind placebo-controlled food challenge, depending on the center. The predetermined objective criteria for a positive oral food challenge were standardized among centers and included urticaria, angioedema, or rhinoconjunctivitis symptoms that persisted for at least 5 minutes or anaphylaxis. To ensure that all participants had confirmed CMA, clinical reactivity to cow’s milk was assessed in participants >1 year of age by food challenge and in those <1 year of age by history of an allergic reaction within 2 months of the study visit and the presence of IgE sensitization to cow’s milk. Blood samples and skin-prick testing were used to confirm the presence of IgE to cow’s milk in all participants. The proportion of participants reacting to 0.5 mg cow's milk protein was estimated with 2-sided exact 95% confidence intervals (CIs).Of the 182 children who met the inclusion criteria, 10 were excluded because they did not have clinical reactivity when undergoing the confirmatory milk challenge. Of the remaining 172 participants with confirmed clinical reactivity to cow’s milk who underwent the ED05 0.5 mg cow’s milk protein oral food challenge, objective symptoms that met the predetermined positive challenge criteria were observed in 7% (95% CI: 3.7% to 11.9%). One participant (17 years old) experienced chest tightness, wheezing, a drop in peak expiratory-flow rate, and truncal erythema and was treated with epinephrine. All other reactions were mild and did not require treatment. No predictors of reactivity to 0.5 mg cow's milk protein were identified.In this study population, 7% of participants reacted to the proposed eliciting dose of 0.5 mg of cow’s milk protein, leading the authors to conclude that 0.5 mg could be a threshold amount of cow’s milk protein to inform food product allergy labeling for cow’s milk content.Although clear food labeling regarding allergen content and risk of allergic reaction is key to ensuring that those with CMA do not overly restrict their diets (while ensuring that they are protected from having a serious allergic reaction), establishing an ED05 to guide food labeling is challenging because of the striking heterogeneity in clinical reactivity among children with CMA. In this study, the authors highlight these challenges because 1 participant experienced an anaphylactic reaction, which translates to 0.5% of the study population. This observation suggests that if foods that contained ≤0.5 mg cow’s milk protein per serving were labeled as safe and children with CMA ate those foods on a regular basis, we might expect to see many cases of anaphylaxis. However, there is a substantial degree of uncertainty around the 0.5% estimate because the 95% CI ranges from 0.01% to 3.2%, highlighting the fact that much larger studies will be needed to have greater certainty about the expected incidence of anaphylaxis to this dose of cow’s milk protein. Additionally, in the study, the researchers found that as many as 12% of similar children would react to 0.5 mg, which, rather than validating an ED05 of 0.5 mg, suggests that the true ED05 may be <0.5 mg. These aforementioned challenges to identifying an ED05 are further complicated by the fact that there were no predictors of reactivity to the 0.5 mg dose. Nevertheless, more work is needed in this area because the current approach to food labeling is confusing and challenging for patients with CMA and their families to navigate.

Community-Based Adverse Food Reactions and Anaphylaxis in Children With IgE-Mediated Food Allergy at Age 6 Years: A Population-Based Study

To investigate the frequency, characteristics, and risk factors of community-based adverse food reactions, including anaphylaxis, among children with food allergies at 6 years of age in a population-based cohort: the HealthNuts study.The HealthNuts study is a longitudinal population-based study of childhood allergic disease in Melbourne, Australia in which researchers originally enrolled 5276 12-month old infants from community immunization clinics. In this report, 3233 children from this cohort are involved who, at 6 years of age, returned for an assessment. An additional 1222 only completed a questionnaire.All caregivers completed questionnaires, and children underwent skin-prick tests to milk, egg, peanut, soy, wheat, sesame, shellfish, cashew, almond, hazelnut and a panel of aeroallergens. Oral food challenges (OFCs) were performed for eligible children. Children were identified as definite or probable food allergy on the basis of skin tests and/or a history of food reactions or results of OFCs. A total of 413 children were eligible for an OFC.A total of 260 children were confirmed as having a food allergy. A total of 44.6% reported an adverse food reaction in the previous 12 months, nearly one-third having >1, with 73% likely immunoglobulin E–mediated. The most common symptoms were hives and vomiting. The most common foods were nuts and egg. One-half of the reactions occurred at home, with restaurants second (11.6%). A total of 28 children reported anaphylactic reactions; nearly one-half were not recognized as such by parents. Tree nuts (mostly cashew) and peanuts accounted for 65% of the anaphylactic reactions. Epinephrine autoinjectors were used in only 13.8% of all anaphylaxis episodes, only 25% of the parent-recognized anaphylaxis episodes, and none of the unrecognized anaphylaxis episodes. There were no risk factors identified for experiencing an adverse food reaction or anaphylaxis, but children with nut allergies were less likely to report an adverse food reaction compared with those without a nut allergy.A high-frequency of adverse food reactions and anaphylaxis in food-allergic children at the age of 6 years occurred in this population-based cohort study. Only one-half of the episodes of anaphylaxis were identified as such, and only 25% of those were treated with an Epinephrine autoinjector. Improved regular education on the prevention of adverse food reactions and recognition and management of anaphylaxis is needed.Pediatricians and other primary care practitioners need to review avoidance measures, possible symptoms or signs of anaphylaxis, and the importance of epinephrine as first-line therapy for anaphylaxis as part of their well-child care for patients with food allergies.

Different Measures of Diet Diversity During Infancy and the Association With Childhood Food Allergy in a UK Birth Cohort Study

To investigate the association between 4 different measures of diet diversity (DD) during infancy and the development of food allergies (FAs) over the first decade of life.Children (n = 969) born in the Isle of Wight (United Kingdom) from 2001–2002.A prospective UK birth cohort was managed through to 10 years of age. The primary exposures of interest were sociodemographic, environmental, and dietary, assessed by questionnaires, including 4 separate parameters of DD. The primary outcome of interest was the development of FA, which was defined as either a positive oral food challenge test result or a positive skin-prick test result with a convincing clinical history.Univariate analysis revealed that increased World Health Organization DD criteria at 6 months (P = .0047), food diversity (P = .0009; P = .0392), food allergen diversity (P = .0048; P = .0233), and fruit and vegetable diversity (P = .0174; P = .0163) at 6 and 9 months, respectively, reduced the odds of FA over the first decade of life. Food allergen diversity at 12 months was significantly associated with a decreased likelihood of having FA at all time points, whereas eczema in the first year was associated with an increased risk of FA. Multivariate analyses, controlling for significant factors, including eczema, revealed that increased food allergen diversity at 6 months (P = .0111) and 12 months (P = .0005) significantly reduced the odds of food allergy over the first 10 years. For each additional food introduced by 6 months, the odds of developing FA over the first decade was reduced by 10.8%. For each additional allergenic food consumed (milk, egg, wheat, fish, soy, peanut, tree nuts, and sesame) by 1 year, there was a reduction of 33.2% in the likelihood of FA over the first 10 years of life.Increased infant diet diversity decreased the likelihood of developing FA, which was sustained over the first decade of life, even after correcting for other significant factors, including eczema.Doctor, what can I do to reduce my infant’s risk of food allergy? It is simple! We can advise not to delay introduction of allergens, and, with this study, we can also advise that a diverse diet is likely beneficial. Is this study solid evidence? The authors attempted to adjust for possible biases, but a controlled trial would be needed to confirm this observational study. Nonetheless, there is a potential rationale for their findings. A diverse diet may expose the infant to a broader microbiome, more allergens early (inducing tolerance), and diverse nutrients that could have positive benefits to immune responses. Food for thought and food for health!

Frequency of Food Allergy in School-Aged Children in Eight European Countries—The EuroPrevall-iFAAM Birth Cohort

The prevalence of food allergy was estimated in children aged 6 to 10 years in 8 European countries.Children from the EuroPrevall birth cohort managed from birth to 2.5 years to prospectively track food allergy onset were reassessed at the ages of 6 to 10 years (N = 6105) in 8 countries (Iceland, United Kingdom, Netherlands, Germany, Poland, Lithuania, Spain, and Greece).School-aged children from the 2005 multicenter European birth cohort were managed by using an online parental questionnaire (n = 6069), clinical visits including a structured interview (n = 2322) regarding previous and current food reactions and food consumption, a physical examination, and skin-prick testing (SPT) (n = 2188). Double-blind placebo-controlled oral food challenges (DBPCFCs) were performed for children (n = 46 of 238 eligible) whose history and SPT (≥3 mm) suggested possible allergies to cow’s milk, hen’s egg, wheat, soy, peanut, hazelnut, white fish, oily fish, or crustaceans. Whole cohort frequency results were extrapolated from fully assessed children.The prevalence of a food allergy to at least 1 confirmed allergen was 0.8%, adjusted to 1.4% to 3.8% by extrapolating to include children without a DBPCFC. Adverse reactions to foods were reported in 16.2% of online questionnaires, similar to face-to-face interviews. Most children consumed cow’s milk, hen’s egg, and wheat products; fewer consumed soy and crustaceans. A total of 10.2% were sensitized to at least 1 food (positive SPT); sensitization was most common to peanut (5.6%) and hazelnut (5.2%). A total of 10.4% were offered DBPCFC, but only 46 children participated. A total of 20 DBPCFCs were positive in 17 children; positive challenges occurred for hazelnut (n = 7), peanut (n = 3), and hen’s egg (n = 1).The estimated prevalence of food allergy in European children was 1.4% to 3.8%. The most common allergies were to peanut and hazelnut.In this study, researchers estimated the true prevalence of sensitization and food allergy in school-aged children in 8 European countries by using a previously established systematic approach to verify food sensitization and allergies in a large number of children from the participating countries. Although a substantial number of participants declined to a DBPCFC, this study reveals the feasibility, utility, and importance of including testing and DBPCFC evaluation in longitudinal food allergy studies.

Review of Ordering Practices for Single-Allergen and Serum-Specific Immunoglobulin E Panel Tests for Food Allergy

To review food allergen serum–specific immunoglobulin E (sIgE) ordering practices, single foods versus food panel, by allergists versus nonallergist providers.Food allergen sIgE laboratory tests performed at a children’s hospital clinical laboratory from January 1 to December 31, 2018.This study was a follow-up retrospective review of food allergen sIgE laboratory tests performed. The test was considered a multiallergen panel if >1 food was included. Ordering practices were compared between allergists and nonallergists. Allergists were made up of both allergists at the institution and community allergists who used that laboratory.A total of 12 345 sIgE tests were ordered by 400 unique practitioners, including 13 allergists at the institution and 41 community allergists. A total of 89% were single-food sIgE tests, and 11% were panels. The top diagnoses associated with sIgE food panels were dermatitis, allergy to other foods, and unspecified abdominal pain. Allergists ordered 8986 tests, of which only 1.2% were panels. Nonallergists ordered 3368 tests, of which 37.5% were panels. The proportion of sIgE tests ordered as panels by community allergists was higher than that by academic allergists (1.9% vs 0.75%). Compared with a similar study from the same center in 2013, there was a 55% decrease in the overall number of panels ordered in 2018.Appropriate diagnosis of an IgE-mediated food allergy requires an appropriate clinical history after ingestion of the suspected food supported by skin-prick tests and/or sIgE tests. The use of sIgE as a screening test is not recommended because of its low positive predictive value. Panels of food sIgE tests are readily available and ordered more by nonallergists than by allergists. Because more individuals will have detectable IgE sensitization than true symptoms, this leads to overdiagnosis and misdiagnosis. This, in turn, can lead to nutritional deficiencies and increased health care costs.Although IgE-mediated food allergies appear to be increasing, overdiagnosis is a concern. Most of these food panels were ordered by nonallergists for complaints not typical of an IgE-mediated food allergy. Families are given lists of positive results without truly understanding the limitations of testing. Trying to determine true allergies versus sensitization without clinical symptoms often requires referral to an allergist who will perform additional tests, including oral food challenges. This can be time consuming and invoke additional costs to the families. Although it is reassuring to see the number is going down, at least at this laboratory, there is still a long way to go regarding educating families and nonallergist providers on the appropriate approaches to diagnosis of IgE-mediated food allergies.