Food-dependent exercise-induced allergic reactions (FDEIA) represent a distinct clinical phenomenon where symptoms arise during exercise following the consumption of specific trigger foods, with the most severe manifestation being anaphylaxis-a condition distinct from typical exercise-induced or food-induced anaphylaxis. In FDEIA, patients can either exercise or tolerate specific foods separately without experiencing any allergic reactions. Diagnosis relies on patient history and provocation testing, requiring rigorous implementation within a supervised hospital environment. Positive symptoms and clinical signs during testing confirm FDEIA, while negative outcomes do not preclude its presence. Exercise stands as the primary trigger, followed by nonsteroidal anti-inflammatory drugs (NSAIDs) and alcohol. The utilization of various protocols for food cofactor challenges to confirm FDEIA yields differing diagnostic outcomes. We highlight the updated concept of food cofactor challenges, incorporating protocols reported in the literature, and summarize current recommendations and comprehensive management approaches for FDEIA patients.

Shellfish is a leading cause of food allergy and anaphylaxis worldwide. Recent advances in molecular characterization have led to a better understanding of the allergen profile. High sequence homology between shellfish species and between shellfish and house dust mites leads to a high serological cross-reactivity, which does not accurately correlate with clinical cross-reactions. Clinical manifestations are immediate and the predominance of perioral symptoms is a typical feature of shellfish allergy. Diagnosis, as for other food allergies, is based on SPTs and specific IgE, while the gold standard is DBPCFC. Cross-reactivity between shellfish is common and therefore, it is mandatory to avoid all shellfish. New immunotherapeutic strategies based on hypoallergens and other innovative approaches represent the new frontiers for desensitization.

The prevalence of food allergies (FA) has increased worldwide over the last few decades. Milk, eggs, and peanuts are among the most common allergens and can cause anaphylaxis. Therefore, we aimed to identify biomarkers that could predict the persistence and/or severity of IgE-mediated allergies to milk, eggs, and peanuts via a systematic review.
This systematic review proceeded according to a protocol registered in the International Prospective Register of Systematic Reviews. Two independent authors extracted studies of interest from PubMed, SciELO, EMBASE, Scopus, and Ebsco databases and assessed their quality using the Newcastle-Ottawa Scale.
We selected 14 articles describing 1,398 patients. Among eight identified biomarkers, total IgE, specific IgE (sIgE), and IgG4 were the most often cited biomarkers of persistent allergies to milk, eggs, and peanuts. Skin prick tests, endpoint tests, and sIgE cutoff levels may predict positive responses to challenges with these foods. The basophil activation test is a biomarker for the severity and/or threshold of allergic reactions to milk and peanuts.
Only a few publications identified possible prognostic indicators of the persistence or severity of FA and outcomes of oral food challenges, indicating that more accessible biomarkers are needed to determine the likelihood of having a severe food allergic reaction.

BACKGROUND: It was reported that prevalence of red meat allergy in children was higher in our country than in western populations. However, the diagnosis of these patients is often delayed. The aim of the study was to present the clinical and laboratory characteristics of our red meat allergy patients.
METHODS: The data were collected retrospectively from the files of children with red meat allergy. Also, 6 adults with red meat allergies were recorded in the families of the children. Patients with symptoms associated with red meat allergy and sensitive to beef or mutton in prick-to-prick tests were recorded.
RESULTS: The median age of the 43 patients was 12 years (2-37), and 51% were male. Most of the patients were children (n=37, 86%). The median age was 10 years in children (2-17), and 54% were male. All of the children had dermatologic manifestations, 51% had respiratory symptoms, and 64% had anaphylaxis upon exposure to red meat. The anaphylaxis history was not associated with demographic, clinical and laboratory data. A total of 63% children had additional allergic diseases, and 75% of them were sensitive to both mutton and beef in prickto- prick tests. The median total IgE level of the children was 327 (20-3550) IU/mL, median eosinophil count was 210/mm < sup > 3 < /sup > (40-990) and mean vitamin D was 13.1 ± 1.2 mcg/L (n=27). Anaphylaxis occurred in 3 of 9 patients who received the open oral food challenge (OFC) test. After OFC, 3 patients continued to eat red meat without issues, and 1 patient was recommended to eat alternatives to red meat.
CONCLUSIONS: Clinical and laboratory findings were heterogeneous in children with red meat allergy. Anaphylaxis risk seems to be higher than other food allergies. OFC test is more helpful in both diagnosis and alternative red meat selection compared to laboratory findings.

BACKGROUND: IgE-mediated egg allergy is a common food allergy worldwide. Patients with egg allergy are known to easily achieve tolerance compared to other allergens such as nuts. Oral food challenge (OFC) is often performed on patients diagnosed with or suspected of having IgE-mediated food allergy, but whether hen\'s egg OFC is useful in IgE-dependent egg allergy patients to avoid complete elimination remains unknown.
METHODS: We identified articles in which OFCs were performed in Japanese patients diagnosed with or suspected of having IgE-mediated egg allergy. We evaluated whether the OFCs were useful to avoid the complete elimination of eggs by assessing the following: (1) the number of patients who could avoid complete elimination; (2) the number of patients who experienced serious adverse events (SAEs); or (3) adverse events (AEs); (4) improvement in quality of life (QOL); and (5) immunological changes.
RESULTS: Fifty-nine articles were selected in the study; all the references were case series or case studies in which OFC was compared to pre-challenge conditions. The overall negative ratio against egg OFC was 62.7%, but an additional 71.9% of OFC-positive patients could take eggs when expanded to partial elimination. Of the 4182 cases, 1146 showed AEs in the OFC, and two cases reached an SAE. Two reports showed an improvement in QOL and immunological changes, although the evidence was weak.
CONCLUSIONS: OFCs against eggs may be useful to avoid complete elimination, but medical professionals should proceed with the test safely and carefully.

Eliciting doses (EDs) (eg, ED01 or ED05 values, which are the amounts of allergen expected to cause objective symptoms in 1% and 5% of the population with an allergy, respectively) are increasingly being used to inform allergen labeling and clinical management. These values are generated from food challenge, but the frequency of anaphylaxis in response to these low levels of allergen exposure and their reproducibility are unknown.
Our aim was to determine (1) the rate of anaphylaxis in response to low-level peanut exposure and (2) the reproducibility of reaction thresholds (and anaphylaxis) at food challenge.
We conducted a systematic review and individual participant data meta-analysis of studies that reported at least 50 individuals with peanut allergy reacting to peanut at double-blind, placebo-controlled food challenge (DBPCFC) and were published between January 2010 and September 2020. Risk of bias was assessed by using National Institute for Clinical Excellence methodologic checklists.
A total of 19 studies were included (covering a total of 3151 participants, 534 of whom subsequently underwent further peanut challenge). At individual participant data meta-analysis, 4.5% (95% CI, 1.9% to 10.1%) of individuals reacted to 5 mg or less of peanut protein with anaphylaxis (moderate heterogeneity [I2 = 57%]). Intraindividual thresholds varied by up to 3 logs, although this variation was limited to a half-log change in 71.2% (95% CI, 56.2% to 82.6%) of individuals. In all, 2.4% (95% CI, 1.1% to 5.0%) of patients initially tolerated 5 mg of peanut protein but then reacted to this dose at subsequent challenge (low heterogeneity [I2 = 16%]); none developed anaphylaxis.
Around 5% of individuals reacting to an ED01 or ED05 level of exposure to peanut might develop anaphylaxis in response to that dose. This equates to 1 and 6 anaphylaxis events per 2500 patients exposed to an ED01 or ED05 dose, respectively, in the broader population of individuals with peanut allergy.

Wheat IgE-mediated food allergy in children is one of the most frequent food allergies in westernized countries, affecting between 0.4 and 1% of children. Although 95% predictive decision points have been determined for major allergens such as peanut, egg, and milk, the diagnostic performances of wheat-specific IgE (sIgE) and wheat component testing are not well established.
The aim of this study was to determine sIgE decision point cutoffs in children with IgE-mediated wheat allergy and provide a review of the literature.
A retrospective review of wheat oral food challenges was performed at the pediatric allergy unit of the University Hospitals of Geneva between 2004 and 2019. Performance characteristics for wheat and ω-5 gliadin sIgE were calculated and positive and negative OFC data were compared using the Mann-Whitney U test.
A wheat sIgE cutoff of 2.88 kUA/L had a sensitivity of 95% (negative decision point), whereas a cutoff of 78.1 kUA/L had a specificity of 95% (positive decision point). When giving equal weight to sensitivity and specificity, the optimal cutoff point for wheat sIgE was 12 kUA/L, which gave a specificity of 70% and a sensitivity of 66.67%.
These findings suggest a high positive decision point for wheat sIgE (78.1 kUA/L). This reinforces the importance of considering OFC in children with IgE-mediated wheat allergy to confirm diagnosis even in patients with relatively high wheat sIgE values, as there is a risk of falsely mislabeling these patients as allergic.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that has been well-characterized clinically, yet it is still poorly understood. Acute FPIES is characterized by vomiting 1-4 h and/or diarrhea within 24 h after ingestion of a culprit food. Chronic FPIES is the result of chronic exposure to an offending food that can result in chronic watery diarrhea, intermittent vomiting, and failure to thrive. FPIES typically presents in infancy and self-resolves by school age in most patients. Adult-onset FPIES is rare, but it has been reported. Cow\'s milk and soy are the most common triggering foods in infants in the US, and as solids are introduced in the diet, FPIES reactions to grains (rice, oat) increase in prevalence. Variability in common trigger foods exists depending on the geographical origin-for example, fish is a frequent trigger in Spanish and Italian patients. Heavy reliance on a detailed history is required for the diagnosis as physical exam findings, laboratory tests, and/or imaging studies are suggestive and not specific for FPIES. Oral food challenges remain the gold standard for confirming diagnosis, and the challenge protocol may be for an individual depending on risk of reaction, prior reaction severity, and positive-specific IgE status. The recent development of diagnostic criteria in 2017 will serve to increase recognition of the disorder and allow for early implementation of management strategies. Acute management during reactions includes IV hydration, anti-emetics, and IV corticosteroids. Reaction prevention strategies include strict food avoidance until the physician deems a food reintroduction challenge clinically appropriate. Future efforts in FPIES research should be aimed at elucidating the underlying disease mechanisms and possible treatment targets.

The role of atopy patch test (APT) in the diagnosis of food allergy (FA) remains largely controversial. In our meta-analysis, we aimed to evaluate the accuracy of APT for diagnosing FA in children.
Pubmed, Embase and Cochrane Library were searched for studies regarding the diagnostic value of APT for FA in children compared to oral food challenge (double-blind placebo-controlled food challenge and/or open food challenge). The last search was conducted on November 11, 2017. Two reviewers independently screened relevant studies and assessed the quality by QUADAS-2. Meta-analysis was performed to calculate the pooled sensitivity, specificity, DOR (diagnostic odds ratio), PLR (positive likelihood ratio), NLR (negative likelihood ratio) with their 95% confidence intervals (CIs). Subgroup analyses were conducted according to different food allergens, atopic dermatitis, gastrointestinal symptoms, and age younger than 3 years.
Forty-one studies were included in the meta-analysis. The pooled sensitivity, specificity, PLR, NLR and DOR were 50.30% (95% CI 48.40%-52.30%), 86.60% (95% CI 85.30%-87.80%), 3.405 (95% CI 2.594-4.470), 0.545 (95% CI 0.469-0.634) and 7.528 (95% CI 5.507-11.206), respectively. However, for children with FA-related gastrointestinal symptoms, the pooled sensitivity and specificity were 57.40% (95% CI 52.10%-62.50%) and 91.50% (95% CI 88.30%-94.10%) respectively.
Our findings suggest that APT is specific but not sensitive for diagnosing FA in children, especially in children with FA-related gastrointestinal symptoms.

BACKGROUND: The diagnosis of IgE-mediated cow\'s milk allergy is often based on anamnesis, and on specific IgE (sIgE) levels and/or Skin Prick Tests (SPT), which have both a good sensitivity but a low specificity, often causing positive results in non-allergic subjects. Thus, oral food challenge is still the gold standard test for diagnosis, though being expensive, time-consuming and possibly at risk for severe allergic reactions.
OBJECTIVE: The aim of the present study was to perform a systematic review of the studies that have so far analyzed the positive predictive values for sIgE and SPT in the diagnosis of allergy to fresh and baked cow\'s milk according to age, and to identify possible cut-offs that may be useful in clinical practice.
METHODS: A comprehensive search on Medline via PubMed and Scopus was performed August 2017. Studies were included if they investigated possible sIgE and/or SPT cut-off values for cow\'s milk allergy diagnosis in pediatric patients. The quality of the studies was evaluated according to QUADAS-2 criteria.
RESULTS: The search produced 471 results on Scopus, and 2233 on PubMed. Thirty-one papers were included in the review and grouped according to patients\' age, allergen type and cooking degree of the milk used for the oral food challenge. In children < 2 years, CMA diagnosis seems to be highly likely when sIgE to CM extract are ≥ 5 KUA/L or when SPT with commercial extract are above 6 mm or Prick by Prick (PbP) with fresh cow\'s milk are above 8 mm. Any cut-offs are proposed for single cow\'s milk proteins and for baked milk allergy in children younger than 2 years. In Children ≥ 2 years of age it is hard to define practical cut-offs for allergy to fresh and baked cow\'s milk. Cut-offs identified are heterogeneous.
CONCLUSIONS: None of the cut-offs proposed in the literature can be used to definitely confirm cow\'s milk allergy diagnosis, either to fresh pasteurized or to baked milk. However, in children < 2 years, cut-offs for specific IgE or SPT seem to be more homogeneous and may be proposed.