Cow's milk allergy (CMA) is a common condition in infants, requiring alternative protein sources in their diets. Soya milk has become a popular substitute, especially in developing countries where it is a more affordable option compared to expensive hypoallergenic feeds for infants with insufficient breast milk supply. However, recent observations have shown an increase in soya cross-allergic reactions among infants with CMA.

To determine how often infants diagnosed with CMA also had soya cross-allergy and to examine the symptoms and outcomes of these infants at 2 years of age.

Data from two pediatric centers were analyzed, looking at clinical records of children under 2 years old diagnosed with CMA from August 2015 to July 2023, divided into two four-year periods.

The records of 432 infants with CMA were analyzed. In the first four-year period from August 2015 to July 2019, 142 infants were studied, with 27 (19%) found to have soya-protein allergy as well. In the second four-year period, a total of 290 infants were studied, and soya allergy was found in 136 babies (47%). This represents a significant increase (P < 0.0001) in cases of soya protein cross-allergy among infants with CMA. The most common symptoms observed were gastroesophageal reflux disorder (39%), followed by failure to thrive, bloody diarrhea, watery diarrhea, and constipation. At 2 years of age, these infants showed significant growth failure compared to infants with CMA only.

In conclusion, this study emphasizes the importance of being cautious when using soy protein in infants with cow's milk protein allergy, especially in areas where cost is a major concern.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated allergy without known biomarkers. We aimed to compare fecal biomarkers related to gut inflammation and immunity in children with FPIES, with resolved FPIES (tolerant), and in matched controls.

Stools were collected from FPIES children on elimination diet, before and after an oral food challenge (OFC) performed to assess their natural tolerance, at the end of a follow-up in tolerant FPIES children, and in matched controls (1:1 ratio). Concentrations of calprotectin, EDN (eosinophilic derived neurotoxin), and secretory IgA (sIgA) underwent comparative paired analysis.

Thirty-eight patients were included (age: 1.3 years old, interquartile range: IQR [0.9-2.0]), of which 22 became tolerant during follow-up. Upon inclusion, allergic patients and controls had similar concentrations of calprotectin (38 μg/g [8-85] vs. 27 μg/g [11-46], p = 0.15) and EDN (504 ng/g [275-1252] vs. 516 ng/g [215-844], p = 0.86). However, concentrations of these inflammatory biomarkers increased transiently after a failed OFC (p < 0.001 and p = 0.01 respectively), without correlating with the severity of an allergic reaction. sIgA were higher in allergic than in tolerant patients: 2224 μg/g [878-3529] vs. 794 μg/g [699-1767] (p < 0.01). Calprotectin, EDN, and sIgA were comparable in tolerant patients and controls. sIgA less than 2637 μg/g had a negative predictive value of 75.3% for the differentiation allergic patients from tolerant patients and controls (area under curve: 0.63, 95% CI: 0.52-0.74).

A few days after an acute allergic reaction, there was no detectable chronic gut inflammation in FPIES. sIgA may be a useful tool for clinicians in timing OFC.

There has been an increase in the prevalence of food allergy among children in the United States. Pediatricians play a pivotal role in caring for children with food allergy, as they are often the first point of contact and enjoy longitudinal relationships with families. In this review, we discuss the epidemiology, risk factors, presentation, diagnosis, and management of food allergy. We also discuss special considerations for patients with food allergy, including nutritional risks and psychosocial stressors that may negatively influence children's wellbeing. Our goal is to provide a concise yet comprehensive guide for general pediatricians so they may feel confident providing high-quality care for patients with food allergy.

Acute and chronic Food Protein-Induced Enterocolitis Syndrome (FPIES) has been well characterized in children; otherwise, neonatal FPIES (N-FPIES) remains poorly understood. In terms of pathophysiology, neonatal FPIES appears to have a more prevalent TH2 response and is characterized by specific clinical features that make the diagnosis challenging. Genetic and environmental risk factors may predispose to the development of FPIES. Recent evidence indicates that a characteristic microbiota signature may lead to barrier dysfunction, reduced regulatory T cells, and abnormal intestinal production of serotonin, responsible for the symptoms of FPIES. Regarding clinical presentation, newborns with FPIES may not fully meet the current guideline's diagnostic criteria at disease onset, being more similar to clinical entity specific of neonatal age than to acute FPIES in infants and children. Hence, differentiation from other neonatal medical and surgical conditions-particularly necrotizing enterocolitis (NEC)-remains a critical challenge for clinicians. This present review highlights our current understanding of N-FPIES, in term of pathophysiology, clinical presentation diagnosis, and treatment strategies. Refining diagnostic criteria for N-FPIES represents a clinical priority to help physicians in diagnosing and managing this challenging condition. Last, but not least, larger clinical trials are needed to optimize treatment practices in term and preterm newborns with FPIES.

Food protein-induced enterocolitis syndrome (FPIES) is the most serious type of non-immunoglobulin E (IgE)-mediated food allergic reaction manifesting as sepsis-like symptom, which can lead to shock. Saccharomyces boulardii (S. boulardii), a probiotic prescribed frequently in clinical settings, has been reported to trigger FPIES in an infant with soy-triggered FPIES. In this report, we describe a new clinical FPIES in which S. boulardii was the sole triggering factor of acute FPIES adverse reaction in seven healthy infants.

Seven FPIES cases triggered by only S. boulardii were gathered from 2011 to the present. None of the patients had previously experienced any allergic reaction to cow's milk, soy, or complementary food. The age of the patients was 4-10-months old, and the symptoms of FPIES developed after ingestion of S. boulardii, which is mostly prescribed for the treatment of gastroenteritis or antibiotic-associated diarrhea. All patients experienced severe repetitive vomiting 1-3 hours after S. boulardii ingestion. Extreme lethargy, marked pallor, and cyanosis were also observed. No IgE-mediated hypersensitivity developed in any patient. Diarrhea was followed by initial intense vomiting in approximately 5-10 hours after S. boulardii ingestion, and only one case showed bloody, purulent, and foul-smelling diarrhea. The patients stabilized quickly, mostly within 6 hours. Symptoms got all improved within 24 hours after discontinuation of S. boulardii.

S. boulardii can be the sole trigger of acute FPIES and be prescribed cautiously even in healthy children without FPIES.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergy characterized by delayed, protracted vomiting and accompanied by lethargy and pallor, usually 1 to 4 hours after ingesting the food allergen. The pathophysiology of FPIES remains unknown, and currently there are no diagnostic biomarkers available to assess disease activity or its resolution. Over the last 2 decades, FPIES has become increasingly recognized in both pediatric and adult patients. Forty years after the initial FPIES description, the first FPIES code appeared in the International Classification of Diseases, Tenth Revision (ICD-10), and the first international consensus guidelines for the diagnosis and management of FPIES were published. On June 22, 2022, the National Institute of Allergy and Infectious Diseases (NIAID) held its first virtual multidisciplinary workshop on FPIES. Various clinical and translational aspects of FPIES as well as important areas of unmet needs were discussed as priorities for future research during this 2-day virtual workshop. Our report provides a summary of content of the workshop, including updated literature on the topic areas, and also provides critical commentary on the state of FPIES.

This European Academy of Allergy and Clinical Immunology (EAACI) guideline provides recommendations for the management of IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Following the confirmation of IgE-mediated food allergy diagnosis, allergen avoidance and dietary advice (with support of a specialised dietitian, if possible) together with the provision of a written treatment plan, education on the recognition of allergic symptoms and prescription of medication including adrenaline using an auto-injector are essential. Patients with significant anxiety and requirement for coping strategies may benefit from support from a clinical psychologist. As immunomodulatory interventions, omalizumab is suggested for treatment of IgE-mediated food allergy in children from the age of 1 and adults; and oral allergen-specific immunotherapy is recommended for children and adolescents with peanut allergy and suggested for milk and egg allergies (generally after 4 years of age for milk and egg). Sublingual and epicutaneous immunotherapy are suggested for peanut allergy but are not yet available at the point of care. Future research into disease modifying treatments for IgE-mediated food allergy are highly needed, with standardised and patient-focused protocols and outcomes.

Non-immunoglobulin E (IgE)-mediated food allergies are characterized by delayed gastrointestinal (GI) manifestations that occur after exposure to an inciting food protein; they include food protein-induced allergic proctocolitis (FPIAP), food protein-induced enteropathy (FPE), and food protein-induced enterocolitis syndrome (FPIES). Although the exact mechanisms underlying these disorders are not well understood, non-IgE-mediated food allergies likely represent a spectrum of disease with shared pathophysiological processes. Typically, these non-IgE-mediated food allergies begin in infancy or early childhood, although FPIES can present across the lifespan, with increasing reports in adults in recent years. Diagnosing non-IgE-mediated food allergies can be challenging due to the lack of noninvasive confirmatory tests or biomarkers for most of these disorders and the non-specific nature of GI symptoms. Thus, the diagnosis is usually made clinically, and relies on a constellation of typical symptoms that improve upon removal of the culprit food. The primary approach to management of FPIAP, FPE and FPIES is avoidance of the triggering food, and a multidisciplinary management approach that includes allergy/immunology may be required to avoid unnecessary food restriction and guide food reintroduction. This review outlines the clinical manifestations, epidemiology, pathophysiology, diagnosis, management, and prognosis of these non-IgE-mediated food allergies.

Allergic inflammation is closely related to the activation of mast cells (MCs), which is regulated by its intracellular Ca2+ level, but the intake and effects of the intracellular Ca2+ remain unclear. The Ca2+ influx is controlled by members of Ca2+ channels, among which calcium voltage-gated channel subunit alpha1 C (CaV1.2) is the most robust. This study aimed to reveal the role and underlying mechanism of MC CaV1.2 in allergic inflammation. We found that CaV1.2 participated in MC activation and allergic inflammation. Nimodipine (Nim), as a strong CaV1.2-specific antagonist, ameliorated allergic inflammation in mice. Further, CaV1.2 activation in MC was triggered by phosphatizing at its Ser1928 through protein kinase C (PKC), which calcium/calmodulin-dependent protein kinase II (CaMKII) catalyzed. Overexpression or knockdown of MC CaV1.2 influenced MC activation. Importantly, CaV1.2 expression in MC had detrimental effects, while its deficiency ameliorated allergic pulmonary inflammation. Results provide novel insights into CaV1.2 function and a potential drug target for controlling allergic inflammation.

Food protein-induced enterocolitis syndrome (FPIES) is a severe type of non-IgE (immunoglobulin E)-mediated (NIM) food allergy, with cow's milk (CM) being the most common offending food. The relationship between the gut microbiota and its metabolites with the inflammatory process in infants with CM FPIES is unknown, although evidence suggests a microbial dysbiosis in NIM patients. This study was performed to contribute to the knowledge of the interaction between the gut microbiota and its derived metabolites with the local immune system in feces of infants with CM FPIES at diagnosis.

Twelve infants with CM FPIES and a matched healthy control group were recruited and the gut microbiota was investigated by 16S amplicon and shotgun sequencing. Fatty acids (FAs) were measured by gas chromatography, while immune factors were determined by enzyme-linked immunosorbent assay and Luminex technology.

A specific pattern of microbiota in the gut of CM FPIES patients was found, characterized by a high abundance of enterobacteria. Also, an intense excretion of FAs in the feces of these infants was observed. Furthermore, correlations were found between fecal bifidobacteria and immune factors.

These fecal determinations may be useful to gain insight into the pathophysiology of this syndrome and should be taken in consideration for future studies of FPIES patients.

The increasing prevalence of food allergy and related pathologies in recent years has underscored the need to understand the factors affecting adverse reactions to food. Food allergy is caused when food-specific IgE triggers the release of histamine from mast cells. However, other food-specific antibody isotypes exist as well, including IgG and IgA. IgA is the main antibody isotype in the gut and mediates noninflammatory reactions to toxins, commensal bacteria, and food antigens. It has also been thought to induce tolerance to food, thus antagonizing the role of food-specific IgE. However, this has remained unclear as food-specific IgA generation is poorly understood. Particularly, the location of IgA induction, the role of T cell help, and the fates of food-specific B cells remain elusive. In this review, we outline what is known about food-specific IgA induction and highlight areas requiring further study. We also explore how knowledge of food-specific IgA induction can be informed by and subsequently contribute to our overall knowledge of gut immunity.

Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE- and non-IgE-mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE- and non-IgE-mediated food allergies and considers the potential future investigations in this context.

Food allergy, referred to as the atypical physiological overreaction of the immune system after exposure to specific food components, is considered one of the major concerns in food safety. The prevalence of this emerging worldwide problem has been increasing during the last decades, especially in industrialized countries, being estimated to affect 6-8% of young children and about 2-4% of adults. Marine organisms are an important source of bioactive substances with the potential to functionally improve the immune system, reduce food allergy sensitization and development, and even have an anti-allergic action in food allergy. The present investigation aims to be a comprehensive report of marine bioactive compounds with verified actions to improve food allergy and identified mechanisms of actions rather than be an exhaustive compilation of all investigations searching beneficial effects of marine compounds in FA. Particularly, this research highlights the capacity of bioactive components extracted from marine microbial, animal, algae, and microalgae sources, such as n-3 long-chain polyunsaturated fatty acids (LC-PUFA), polysaccharide, oligosaccharide, chondroitin, vitamin D, peptides, pigments, and polyphenols, to regulate the immune system, epigenetic regulation, inflammation, and gut dysbiosis that are essential factors in the sensitization and effector phases of food allergy. In conclusion, the marine ecosystem is an excellent source to provide foods with the capacity to improve the hypersensitivity induced against specific food allergens and also bioactive compounds with a potential pharmacological aptitude to be applied as anti-allergenic in food allergy.

Food protein-induced enterocolitis syndrome (FPIES) is being increasingly recognized as a non-IgE-mediated food allergy; however, it remains unclear if and how the presentation, diagnosis, and management of this disease has changed in recent years.

To reappraise the FPIES cohort at a large US pediatric tertiary referral center.

We performed a retrospective chart review of pediatric patients with FPIES (International Classification of Diseases, Tenth Revision code K52.21) diagnosed in our allergy/immunology clinics between 2018 and 2022.

There were 210 children diagnosed with FPIES. Most were White (73.8%), non-Hispanic (71.4%), and male (54.3%) with private insurance (77.6%). Cow's milk was the most common food trigger (35.2%), with the earliest median age of onset of 5 months. The atypical FPIES rate was 13.8%. FPIES was accurately diagnosed in 54.3% at the first medical contact. The oral food challenge pass rate was 73.5%. The rate of trigger resolution at 36 months was 77%.

By comparing trends from a previous and current FPIES cohort, we were able to assess the potential impact of various guidelines and practice changes on the diagnosis and management of FPIES at our center. Milk and oat surpassed rice as the most common FPIES triggers; peanut and egg emerged as new FPIES triggers; there was a shorter time to diagnosis and an increased rate of atypical FPIES. Our findings reflect earlier recognition of FPIES and prompt allergy/immunology referral from community physicians, implementation of recent medical society guidelines for infant feeding practices, and growing clinical expertise of allergists at our center.

Food protein-induced enterocolitis syndrome (FPIES), a non-IgE-mediated allergy, primarily affects infants and young children. Whether and when tolerance develops seems to vary among populations and trigger foods.

This study aimed to evaluate tolerance development and its assessment in a Swedish cohort.

This was a prospective follow-up study of a Swedish cohort of 113 children, followed at 25 pediatric departments, with acute FPIES. Data on oral food challenges and FPIES resolution were collected through chart reviews and, if incomplete, supplemental caregiver interviews.

The median age at last follow-up was 5.6 years (range: 8.7 months to 16.5 years). Eighty-three children (73%) developed tolerance to 96 of 137 (70%) foods: 93% for cow's milk, 92% for oat, and 46% for fish. The median age when tolerance was developed was 36.0 months (interquartile range: 23.7-48.2 months): 24.4 months for cow's milk, 30.1 months for oat, and 49.4 months for fish. Tolerance was determined in hospital in 45% of cases. Five percent demonstrated allergic sensitization to their FPIES trigger food. Age at tolerance development did not differ between sensitized and nonsensitized patients.

Most of the children in this Swedish cohort with FPIES achieved tolerance before age 4 years. Cow's milk- and oat-induced FPIES had similar remission patterns, with early resolution. Development of tolerance to fish occurred significantly later compared with all other FPIES-inducing foods.

Breastfeeding is the most important nutrition source for infants. However, managing breastfed infants with signs and symptoms related to food allergy can be difficult. Many studies have shown the presence of different food allergens in breast milk, but the clinical role of these antigens in human milk is still much debated. Milk is the main suspect in exclusively breastfed infants with signs and symptoms attributable to food allergy, even if other foods may be responsible. This narrative review analyzes the recommendations provided by international guidelines to determine the diagnosis and management of IgE-mediated and non-IgE-mediated food allergies in exclusively breastfed infants. Dietary restrictions in lactating mothers of infants with suspected FA are usually not necessary. Only in the very few cases where significant allergy signs and symptoms occur in the infant during exclusive breastfeeding should the lactating mother follow an elimination diet for the suspected food for a short period.

Some patients with food protein-induced enterocolitis (FPIES)-like allergy do not completely fulfill the diagnostic criteria of the international consensus guideline for FPIES. However, it is unclear whether such FPIES-like patients represent a completely different population from FPIES.

This study aimed to clarify differences in characteristics between patients with FPIES who fully met diagnostic criteria and those who partly met them.

This was a cross-sectional study using data at the time of registration in multicenter, prospective studies of patients with FPIES in Japan. Children who had delayed emesis within 1 to 4 hours and/or diarrhea within 5 to 10 hours after ingestion of food were recruited between March 2020 and February 2022. We examined their compatibility with the diagnostic criteria of the international consensus guideline and their detailed clinical characteristics, including trigger foods, the serving size that elicited symptoms, and antigen-specific IgE antibody titers.

Of the 225 patients with FPIES, 140 fully met the diagnostic criteria whereas 79 patients did not fully meet them but demonstrated reproducible symptoms. The frequencies of pallor, lethargy, and diarrhea were significantly higher in those who met the criteria fully, whereas the age at onset, trigger foods, comorbidity, and perinatal information were comparable. Analysis of patients with FPIES to hen's egg revealed significantly higher levels of egg white- and egg yolk-specific IgE in patients who partly met criteria, whereas the serving size eliciting symptoms was comparable.

Patients who partly met the diagnostic criteria may have a milder phenotype of FPIES, but this needs to be validated in further studies using biomarkers reflecting the pathophysiology.

Food allergy can often cause a significant burden on patients, families, and healthcare systems. The complexity of food allergy management requires a multidisciplinary approach involving different types of healthcare providers, including allergists, dieticians, psychologists, nurses, family practitioners and, of particular relevance for this article, pediatric primary caretakers. Pediatricians may be the first-line healthcare providers for food allergy: strategies for management and guideline adherence have been highlighted.

This review article summarizes the up-to-date recommendations on the role of pediatricians in the diagnosis, management, and prevention of IgE-mediated food allergy. Early introduction of allergenic foods like peanut is known to be of importance to reduce the development of peanut allergy in infants, and pediatricians are essential for educating and supporting parents in this decision. In scenarios of limited allergist availability, as is often the case among rural, Medicaid and minority populations, pediatricians can assist in the evaluation and management of food allergy, and provide action plans, education and counselling for patients and families.

Pediatric primary caretakers play a key role in the diagnosis, management, and prevention of IgE-mediated food allergy. As more diagnostic tools and therapies in food allergy become available, the need for a multidisciplinary team is paramount to optimize patient care.

The association between food protein-induced enterocolitis syndrome (FPIES) and wheat ingestion in children with celiac disease is unknown at this time.

We present seven cases of children with celiac disease who presented with symptoms of wheat-triggered acute FPIES (a-FPIES). An oral food challenge (OFC) with wheat allergen followed by 4 h of observation was performed. Activation of innate system cells was measured at baseline (T0), during symptoms (Ts), and 4 h after symptom onset (Ts + 4). A panel of human inflammatory cytokines was also performed.

All patients reacted to the first allergen dose. Three patients experienced a decrease of 30 mm Hg in systolic blood pressure and tachycardia and required hemodynamic resuscitation. Neutrophilia and a decrease in eosinophil count were evident at 4 h after symptom onset. At 4 h after symptom onset, cytokines (IL-6 and IL-8, and to a lesser degree, IL-10) were elevated.

In a small sample of celiac patients with wheat exposure in an OFC, symptoms and acute immunological changes in serum inflammatory cytokine profile were consistent with a-FPIES.

Food protein-induced enterocolitis syndrome (FPIES) is a food allergy that results in repetitive vomiting, lethargy, and pallor within 1 to 4 hours of food ingestion. One of the issues in its management is the introduction of new foods. Over the past 25 years, suggestions have been made mainly based on the likelihood that a given food family could induce an episode of acute FPIES. Thus, foods have been categorized into low, moderate, and high risk. The suggestion was always to postpone the introduction of moderate- or high-risk foods, leaving the decision whether to introduce them at home or in hospital to the doctor. These suggestions were designed for all children with acute FPIES, regardless of their geographical area. However, it is true that these suggestions are the result of expert opinion. In recent years, studies have been published that have shown that the risk category of foods varies according to geographical area and so does the prevalence of single FPIES versus multiple FPIES. For this reason, we believe that the introduction of new foods in the child with acute FPIES can and should be tailored according to the geographical area.

Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE) cell mediated food allergy that can cause severe symptoms and is considered an allergic emergency.

To describe FPIES epidemiology and appraise the approach to diagnosis and management.

A review of the relevant articles published in the peer-reviewed journals since the publication of the First International FPIES Consensus Guidelines in 2017.

FPIES is estimated to affect 0.51-0.9% of children and 0.22% of adults in the United States. It typically presents with protracted, projectile vomiting, which occurs within 1-4 hours of ingesting culprit foods, sometimes followed by diarrhea within 24 hours of ingestion. In ∼15-20% of severe cases, patients go into hypovolemic or distributive shock. In chronic FPIES, infants may have failure to thrive and weight loss. The most common triggers include cow's milk, oat, rice, and avocado, with egg and peanut being more frequently reported. Examples of other common fruit and vegetable triggers include banana, apple, and sweet potato. FPIES can be classified into acute, chronic, adult-onset, or atypical subtypes. FPIES is associated with comorbid atopic conditions of IgE-mediated food allergy, atopic dermatitis, asthma, allergic rhinitis, and eosinophilic esophagitis. The natural history of infantile FPIES is generally favorable, with the exception of fish FPIES. Seafood FPIES in adults has low rates of resolution over 3-5 years. Correctly identifying FPIES can be challenging because there are no specific biomarkers for diagnosis and the constellation of symptoms may mimic those of infectious enteritis or sepsis. Management relies on dietary food avoidance, periodic re-evaluations for tolerance with oral food challenges, and management of acute reactions with rehydration and antiemetic ondansetron. Although the pathophysiology of FPIES remains poorly understood, underlying mechanisms such as cytokine release, leukocyte activation, and impaired gastrointestinal mucosal barrier function may act as cornerstones for further research.

Prevention, laboratory diagnostic testing, and strategies to accelerate tolerance development are urgent unmet needs in FPIES.

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.

Food protein-induced enterocolitis syndrome (FPIES) is a form of non-IgE mediated food allergy that presents with delayed gastrointestinal symptoms after ingestion of the trigger food. The data regarding FPIES are sparse, despite being recognized as a distinct clinical entity. This narrative review presents the characteristics of this disorder in the pediatric population, as well-standard diagnostic and management protocols. FPIES can be classified into acute and chronic subtypes, and some cases may develop into an IgE-mediated allergy. Given that skin prick tests and specific IgE levels are negative in the majority of cases, diagnosis relies on clinical history and oral food challenges. Management involves elimination diets, assessment of tolerance through oral food challenges, and rehydration in the event of a reaction. Future research should focus on improving diagnostic methods, illustrating underlying pathogenesis and biomarkers, and assessing long-term natural history. Increased knowledge and awareness for FPIES are required.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy treated by trigger food avoidance and supportive care. Whether the prevalence of different trigger foods is changing with evolving food introduction patterns is unknown. The rate and nature of subsequent reactions after initial diagnosis have not been fully studied.

We sought to characterize how trigger foods have changed over time and investigate the nature of subsequent reactions after initial diagnosis.

We collected data regarding patients' FPIES reactions from 347 patients seen in the University of Michigan Allergy and Immunology clinic for FPIES from 2010 to 2022. Inclusion criteria consisted of pediatric patients diagnosed with FPIES by an allergist based on international consensus guidelines.

Most foods including less commonly cited FPIES triggers increased in frequency over time. The most common index trigger was oat. A total of 32.9% (114 of 347) patients experienced a subsequent reaction after education on trigger avoidance and safe home introduction of new foods, with 34.2% (41 of 120) of subsequent reactions to new triggers at home and 45% (54 of 120) to known triggers at home. Of patients reacting subsequently, 28% (32 of 114) experienced a subsequent reaction necessitating an emergency department visit. The most common new subsequent reaction triggers were egg and potato, whereas peanut most commonly triggered reactions on oral food challenge.

The risk profile of FPIES triggers may be evolving over time, though high-risk FPIES foods remain common. The subsequent reaction rate after counseling indicates that home food introduction poses risk. This study highlights the need for improved safety of new food introduction and/or prediction methods for FPIES to help prevent potentially dangerous home FPIES reactions.

Fish is one of the "big nine" foods triggering allergic reactions. For this reason, fish allergens must be accurately specified on food labels. Fish allergy affects less than 1% of the world population, but a higher prevalence is observed in pediatric cohorts, up to 7%. Parvalbumin is the main fish allergen found in the muscles. In childhood, sensitization to fish allergens occurs most frequently through the ingestion of fish, rarely transcutaneously or by inhalation. Fish allergy symptoms usually appear within two hours of the allergen contact. The diagnosis begins with the collection of the history. If it is suggestive of fish allergy, prick tests or the measurement of serum-specific IgE should be performed to confirm the suspicion. The oral food challenge is the gold standard for the diagnosis. It is not recommended in case of a severe allergic reaction. It is important to make a differential diagnosis with anisakiasis or scombroid poisoning, which have overlapping clinical features but differ in pathogenesis. Traditionally, managing fish allergy involves avoiding the triggering species (sometimes all bony fish species) and requires an action plan for accidental exposures. The present review will analyze IgE- and non-IgE-mediated fish allergy in children from epidemiology, pathogenesis to clinical features. Moreover, clinical management will be addressed with a particular focus on potential nutritional deficiencies.

Introduction: there is an emerging current necessity of valid questionnaires, encompassing most of food, beverages, diseases, signs and symptoms currently related to the pathogenesis of adverse reactions to foodstuffs (ARFS) in the Spanish population. Objectives: this study aimed to design and validate two questionnaires to assess ARFS in the Spanish population, Food and Beverages Frequency Consumption Questionnaire to Identify Adverse Reactions to Foodstuffs (FBFC-ARFSQ-18); and Pathologies and Symptomatology Questionnaire associated with Adverse Reactions to Foodstuffs (PSIMP-ARFSQ-10). Methods: both questionnaires were designed adapting questionnaires from the literature; and validated, using the expert judgment method, in five phases: questionnaires development, pilot test and reliability, content validity, face validity, and ethical considerations. Questionnaires were developed using the REDCap™ tool hosted at the Universidad Politécnica de Madrid. A total of 20 Spanish experts evaluated the questionnaires. Cronbach's alpha reliability coefficients were calculated using SPSS version 25.0 (IBM Corp., Armonk, NY-USA) and Aiken's V coefficient values were calculated using ICaiken.exe (Visual Basic 6.0, Lima-Perú). Results: a final construct of questions was designed, ensuring no overlap, for FBFC-ARFSQ-18 and PSIMP-ARFSQ-10. Cronbach's alpha reliability coefficients were 0.93 and 0.94; and Aiken's V coefficient values were 0.90 (0.78-0.96 CI) and 0.93 (0.81-0.98 CI) for FBFC-ARFSQ-18 and PSIMP-ARFSQ-10, respectively. Conclusions: both validated questionnaires could be used to analyze the association between certain food and beverages consumption with ARFS, such as food allergies and food intolerances; also, to investigate the link between some specific diseases, signs and symptoms with ARFS.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy that has a cumulative incidence of 0.015 to 0.7% in infants [1]. The most common allergens causing FPIES reactions include cow's milk, followed by soy, grains, and rice [1, 3]. Increasing clinical awareness of FPIES has resulted in the expansion of emerging triggers of FPIES, including fruit antigens.

We describe an infant diagnosed with FPIES to prune.

Fruit allergens are an emerging group of triggers for FPIES, both in their fresh and dried forms. To our knowledge, this case is the first presentation of FPIES to prunes (dehydrated plum). This case highlights that careful history taking can avoid unnecessary investigations and delay in diagnosing FPIES.

Food allergy is an immune-mediated disease that can result in considerable morbidity and even mortality, with a significant negative impact on patients' quality of life. It is characterized by allergic symptoms that can occur shortly after a relevant food allergen ingestion, or can be delayed or chronic, which make it more difficult for diagnosis. The symptoms of this disease can range from mild to severe, and rarely can cause anaphylaxis, a life-threatening allergic reaction. The prevalence of non-immunoglobulin E (IgE)-mediated food allergy is poorly established outside of cow's milk allergy, with an adjusted incidence ranging between 0.13% and 0.72%. Several disorders are classified as non-immunoglobulin E (IgE)-mediated food allergies that predominantly affect the gastrointestinal tract including food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), food protein-induced allergic enteropathy (FPE), and food protein-induced dysmotility disorders (GORD and constipation). Eosinophilic esophagitis (EoE) is listed in this group, even though it considered by some authorities to be mixed reaction with both IgE and cell-mediated immune response to be involved in the reaction. The most common types of non-IgE-mediated food allergy are food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP). These disorders typically present in infancy and are often triggered by cow's milk protein. Patients with FPIES present with profuse emesis and dehydration, while FPIAP patients present with hematochezia in otherwise healthy infants. Since there are no specific confirmatory non-invasive diagnostic laboratory tests, the diagnosis is usually made clinically when typical symptoms improve upon the removal of the culprit food. Food reintroduction should be attempted, when possible, with documentation of symptoms of relapse to confirm the diagnosis. The management includes dietary avoidance, supportive treatment in the case of accidental exposure, and nutritional counseling. This review focuses on the clinical manifestations, epidemiology, management, and recent guidelines of the most common non-IgE-mediated food hypersensitivity disorders (FPIES, FPIAP, and FPE).

The prevalence and awareness of food allergy (FA) among US adults is arguably at a historical high, both with respect to primary immunoglobulin E-mediated food hypersensitivity and other food-triggered conditions that operate through a variety of immunologic mechanisms (eg, pollen-FA syndrome, alpha-gal syndrome, food protein-induced enterocolitis syndrome, eosinophilic esophagitis). Worryingly, not only are many adults retaining childhood-onset food allergies as they age into adulthood, it seems that many adults are experiencing adult-onset allergies to previously tolerated foods, with correspondingly adverse physical, and psychological health impacts. Consequently, this review aims to summarize what is currently known about the epidemiology and population-level burden of FA among adult populations in North America and around the globe. This article also provides insights into the natural history of these conditions and what we need to know as we look to the future to support effective care and prevent FA.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with a typical onset in infancy. Its symptoms are distinct from those of IgE-mediated food allergies and include severe repetitive vomiting, lethargy, and pallor. FPIES reactions are associated with TH17 cytokines and a systemic innate immune activation; however, the link between immune activation and symptoms is poorly understood.

Our aim was to use an untargeted metabolomics approach to identify novel pathways associated with FPIES reactions.

Serum samples were obtained before, during, and after oral food challenge (OFC) (10 subjects with FPIES and 10 asymptomatic subjects), and they were analyzed by untargeted metabolomics. Two-way ANOVA with false discovery rate adjustment was used for analysis of metabolites. Stomach and duodenal biopsy specimens from non-FPIES donors were stimulated with adenosine in vitro and serotonin measured by immunoassay.

The levels of a total of 34 metabolites, including inosine and urate of the purine signaling pathway, were increased during OFCs performed on the patients with symptomatic FPIES compared with the levels found for asymptomatic subjects. Expression of the purine receptors P2RX7 and P2RY10 and the ectonucleotidase CD73 in peripheral blood was significantly reduced after OFC of the patients with FPIES. The level of the serotonin metabolite 5-hydroxyindoleacetate was significantly elevated after reaction. Adenosine stimulation of gastric and duodenal biopsy specimens from FPIES-free donors induced a significant release of serotonin, suggesting a link between purinergic pathway activation and serotonin release.

Activation of the purinergic pathway during FPIES reactions provides a possible mechanism connecting inflammation and vomiting by triggering serotonin release from gastric and duodenal mucosa.

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.