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Food protein-induced enterocolitis syndrome caused by solid foods (Solid-FPIES) is a non-immunoglobulin E-mediated allergic disease characterized by delayed gastrointestinal symptoms. An oral food challenge (OFC) test, although necessary, can be inconclusive in cases with mild symptoms. Moreover, limited diagnostic marker availability highlights the need for novel surrogate markers. We aimed to examine the efficacy of fecal hemoglobin (FHb), lactoferrin (FLf), and calprotectin (FCp) over time in evaluating gastrointestinal inflammation degree in Solid-FPIES. This observational study included 40 patients and 42 episodes at Juntendo University Hospital and affiliated hospitals between October 2020 and March 2024 categorized into FPIES (12 patients with 11 egg yolk, 1 fish, and 1 soybean episodes), control (14 patients with 15 episodes), and remission (14 patients). Fecal tests were performed for 7 days following antigen exposure. The ratios of each value were divided by the baseline value and analyzed over time course. The FPIES group had significantly higher peak ratios of all fecal markers than the control group (p < 0.01). The median FHb, FLf, and FCp ratios were 3.25, 9.09, and 9.79 in the FPIES group and 1.08, 1.29, and 1.49 in the control group, respectively. In the remission group, several patients had fluctuating fecal markers despite negative OFC, and one patient was diagnosed with FPIES by OFC with increased load. Receiver operating characteristic curve analyses revealed high diagnostic performance for each fecal marker in FPIES. Sequential fecal marker examination proved valuable in diagnosing Solid-FPIES and evaluating the degree of gastrointestinal inflammation. [ABSTRACT FROM AUTHOR]

Introduction: The association between food protein-induced enterocolitis syndrome (FPIES) and wheat ingestion in children with celiac disease is unknown at this time. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Food protein-induced enterocolitis syndrome caused by solid foods (Solid-FPIES) is a non-immunoglobulin E-mediated allergic disease characterized by delayed gastrointestinal symptoms. An oral food challenge (OFC) test, although necessary, can be inconclusive in cases with mild symptoms. Moreover, limited diagnostic marker availability highlights the need for novel surrogate markers. We aimed to examine the efficacy of fecal hemoglobin (FHb), lactoferrin (FLf), and calprotectin (FCp) over time in evaluating gastrointestinal inflammation degree in Solid-FPIES. Methods: This observational study included 40 patients and 42 episodes at Juntendo University Hospital and affiliated hospitals between October 2020 and March 2024 categorized into FPIES (12 patients with 11 egg yolk, 1 fish, and 1 soybean episodes), control (14 patients with 15 episodes), and remission (14 patients). Fecal tests were performed for 7 days following antigen exposure. The ratios of each value were divided by the baseline value and analyzed over time course. Results: The FPIES group had significantly higher peak ratios of all fecal markers than the control group (p

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by gastrointestinal symptom onset within 1–4 hours from trigger food ingestion. In the literature, some authors have previously described the possibility that a patient with FPIES may develop an IgE-mediated allergy to the same trigger food, especially cow's milk (CM). Case Presentation: We reported five cases of CM-FPIES converting to IgE-mediated CM allergy presented at our tertiary pediatric Allergy Unit and performed a review of the literature, aiming to characterize the clinical features of patients who are at risk of developing such conversion. Conclusions: This phenomenon raises the question of whether IgE-mediated and non-IgE-mediated allergies represent a spectrum of the same disease and highlights the need for further investigation to understand the pathophysiological mechanisms of this process. [ABSTRACT FROM AUTHOR]

Background: Food protein–induced enterocolitis (FPIES) is a non–IgE-mediated food allergy that is becoming increasingly recognized in adults. The time between age at symptom onset (ASO) and age at diagnosis (AD and factors affecting this gap have not been fully studied. Objective: We sought to investigate the latency between ASO and AD in adults with FPIES. We also sought to evaluate whether those patients with symptom onset in earlier years and those with comorbid gastrointestinal (GI) disease had greater mean latency. Methods: We conducted a retrospective chart review for patients with FPIES who were seen in the University of Michigan Allergy and Immunology clinic from 2015 to 2022. Patients aged 18 years and older and diagnosed with FPIES by an allergist were included (N = 19). The data collected included characteristics of the patients’ prior FPIES reactions and medical history. Results: The median age of onset of FPIES symptoms was 26 years, and the median AD was 35 years. The median difference between ASO and AD was 10 years; this difference was statistically significant according to a paired t test (P = .003). There was a negative correlation of –0.99 between year of symptom onset and latency between ASO and AD (P < .0001). Those patients with previously diagnosed GI conditions had a higher mean latency between ASO and AD than those without GI conditions did (P = .124). Conclusions: We noted a gap between ASO and AD in adults with FPIES. This gap may be due to underrecognition of adult FPIES in the past given the negative correlation with mean latency between ASO and AD. Furthermore, comorbid GI illnesses may be masking FPIES symptoms in adults, thus delaying diagnosis.

Introduction: Food protein-induced enterocolitis syndrome (FPIES) is a form of non-IgE-mediated gastrointestinal food allergy. FPIES is considered a rare food allergy disorder and is often under-recognized. Therefore, clinicians should have a better understanding of its manifestations and maintain a high index of suspicion for a correct diagnosis. To this end, information about differences in the characteristics of caregiver-reported and physician-diagnosed FPIES is important. Methods: The present, national, multicentric, prospective birth cohort study, called the Japan Environment and Children's Study (JECS), enrolled a general population of 104,062 fetal records. The characteristics of FPIES in 1.5-year-old children were categorized as cases reported by caregivers or as those diagnosed by a physician using questionnaire data. Results: The prevalence of caregiver-reported and physician-diagnosed FPIES cases was 0.69% and 0.06%, respectively. Among the former, the most common causative food was hen's egg (HE), and the second most common causative food was cow's milk (CM) (51.0% and 17.1% of patients responded to HE and CM, which accounted for 46% and 15% of all the causative foods, respectively). Conversely, among the physician-diagnosed cases, the most common causative food was CM followed by HE (57.7% and 36.5% of patients responded to CM and HE, which accounted for 46% and 29% of all the causative foods, respectively). CM accounted for a significantly higher proportion of causative foods in physician-diagnosed FPIES while HE accounted for a significantly higher proportion of caregiver-reported FPIES (p < 0.05). Conclusion: A discrepancy was found in reports of the most common causative food between caregiver-reported and physician-diagnosed cases of FPIES. [ABSTRACT FROM AUTHOR]

Purpose of Review: Food allergies are immune-mediated, complex disorders, which are the source of increasing health concern worldwide. The goal of this review is to present an updated summary of the food allergy (FA) burden among children and adults across different populations, focusing on research from the past 5 years. Recent Findings: FAs impact a growing number of global residents—particularly those residing in higher-income, industrialized regions. Moreover, growing epidemiologic evidence suggests that the population health burden of non-IgE-mediated FAs, such as food protein-induced enterocolitis syndrome, may also be higher than previously reported. Summary: FA is a complex trait that impacts infants, children, as well as adults across the globe. The population health burden of both IgE- and non-IgE-mediated FAs is likely to grow in the absence of rapid advances and widespread implementation of effective FA prevention and treatment interventions. Systematic epidemiological research initiatives are needed, both nationally and globally, to better understand and reduce the burden of these allergic diseases. [ABSTRACT FROM AUTHOR]

This article discusses the diagnosis of paediatric mild acute Food Protein-Induced Enterocolitis Syndrome (FPIES). The current diagnostic criteria for FPIES may not accurately diagnose milder cases of the disease. The article proposes new criteria for the diagnosis of paediatric mild acute FPIES. The study retrospectively reviewed cases of paediatric mild acute FPIES and found that the new diagnostic and suspicion criteria were able to identify all 15 cases. The article provides detailed information on the patients' demographics and symptoms. These new diagnostic and suspicion criteria aim to include all mild forms of pediatric acute FPIES and may be useful for community pediatricians, although they have not been prospectively validated and are based on expert opinion. [Extracted from the article]

Continuous intake of allergenic food is a safe and efficient treatment strategy for patients with a prolonged course of acute food protein–induced enterocolitis syndrome. The initial dose, dose escalation rate, and starting age for continuous allergenic food intake need further clarification.

Abstract Background Food protein-induced enterocolitis syndrome (FPIES) is a delayed, non-IgE-mediated food allergy. This syndrome was once thought to be rare, but emerging literature suggests an increasing incidence along with more foods being implicated. Also, with the introduction of guidelines on early peanut introduction, peanut-induced FPIES seems to be increasing in Australia and USA. Although most patients are diagnosed with FPIES within the first year of life, most commonly with food triggers to cow’s milk or soy, other phenotypes exist in comparison to this classic presentation. In this case report, we present a patient with late onset of acute FPIES at age 3 to walnut. Case Presentation We describe a case of FPIES in a 12-year-old boy who had recurrent episodes of repetitive emesis, that began at age 3, each time after consuming walnuts. Mom does not give a history of intentional feeding (or avoidance) of walnut and/ or pecans. She also described possible reactions with pine nuts and macadamia. He was assessed with an oral food challenge to walnut, which triggered an episode of acute FPIES. He developed vomiting with onset 2 h post-ingestion, pallor, lethargy, and required an emergency department visit for anti-emetic medications and oral rehydration therapy. He improved on the therapy and now avoids cashew, pistachio, hazelnuts, walnuts, pecans, pine nuts, and macadamia nuts. Conclusions This case report adds to the limited literature that exists on culprit food allergens in FPIES. We present an acute FPIES triggered by the ingestion of walnuts. The diagnosis, common food triggers, and natural history of FPIES are described. There remains a lack of information on the natural history of FPIES, especially towards uncommon food triggers and on FPIES that present beyond infancy.

Objective: Food protein-induced enterocolitis syndrome (FPIES) is an uncommon, non-IgE (immunoglobulin E) -mediated food allergy that mainly affects infants and young children. Our study aims to evaluate the etiology, clinical phenotypes, and tolerance status of our cases with FPIES. Method: The file records of the patients who were followed up with the diagnosis of FPIES in the Departments of Pediatric Allergy and Gastroenterology of our hospital, between September 2016 and June 2022 were examined, and families who could not attend follow-up visits regularly were contacted by phone. Results: Twelve (66.66%) of 18 cases with a mean age of admission of 33.0+-27.5 (2-108) months were boy. The triggers of FPIES were fish in 66.66%, cow's milk in 16.66%, eggs in 5.55%, eggs and milk in 5.55%, and potato in 5.55% of the patients. While 94.44% of the cases had acute FPIES, and 44.4% of them had early-onset (

Background: There are no reports on the relationship between food protein–induced enterocolitis syndrome (FPIES) diagnosis and procalcitonin levels. Objective: Our study sought to demonstrate a correlation between the presence or absence and severity of FPIES symptoms and postemetic procalcitonin levels. Methods: The subjects were 53 patients with FPIES (44 with hen’s egg allergy, 4 with milk allergy, 4 with wheat allergy, and 3 with soy allergy), who collectively underwent a total of 75 oral food challenges (OFCs). Procalcitonin levels at 5 hours after antigen ingestion were compared between patients with a positive OFC result and those with a negative OFC result and between patients who experienced mild or moderate events and those who experienced severe events. Results: At 5 hours after ingestion of the causative food, the median procalcitonin levels in patients with a negative OFC result, patients who experienced a mild or moderate event, and patients who experienced a severe event were 0.02, 0.03, and 0.16 ng/mL, respectively. The procalcitonin level was significantly higher in the groups with a positive OFC result than in the groups with a negative OFC result (P < .001), and it was significantly higher in those who experienced severe events than in those who experienced mild or moderate events (P = .012). Conclusion: Measurement of procalcitonin levels has the potential to provide a quantitative and objective assessment of FPIES diagnosis and severity.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a delayed, non-IgE-mediated food allergy. This syndrome was once thought to be rare, but emerging literature suggests an increasing incidence along with more foods being implicated. Also, with the introduction of guidelines on early peanut introduction, peanut-induced FPIES seems to be increasing in Australia and USA. Although most patients are diagnosed with FPIES within the first year of life, most commonly with food triggers to cow's milk or soy, other phenotypes exist in comparison to this classic presentation. In this case report, we present a patient with late onset of acute FPIES at age 3 to walnut. Case Presentation: We describe a case of FPIES in a 12-year-old boy who had recurrent episodes of repetitive emesis, that began at age 3, each time after consuming walnuts. Mom does not give a history of intentional feeding (or avoidance) of walnut and/ or pecans. She also described possible reactions with pine nuts and macadamia. He was assessed with an oral food challenge to walnut, which triggered an episode of acute FPIES. He developed vomiting with onset 2 h post-ingestion, pallor, lethargy, and required an emergency department visit for anti-emetic medications and oral rehydration therapy. He improved on the therapy and now avoids cashew, pistachio, hazelnuts, walnuts, pecans, pine nuts, and macadamia nuts. Conclusions: This case report adds to the limited literature that exists on culprit food allergens in FPIES. We present an acute FPIES triggered by the ingestion of walnuts. The diagnosis, common food triggers, and natural history of FPIES are described. There remains a lack of information on the natural history of FPIES, especially towards uncommon food triggers and on FPIES that present beyond infancy. [ABSTRACT FROM AUTHOR]

Aim: To describe clinical presentation and development of tolerance among children with Food protein‐induced enterocolitis syndrome (FPIES) in a population in northern Sweden. Methods: A retrospective review of medical records of children presenting with FPIES symptoms from 1 January 2004, to 31 May 2018. Results: Sixty children (65% boys) with FPIES were included. The estimated incidence gradually increased to 0.45% in 2016–2017. The most common food triggers were cow's milk (40%), fish (37%) and oat (23%). Symptoms presented in 31 (60%) children before 6 months and in 57 (95%) before 1 year of age. The median age for FPIES diagnosis was 7 (range 3–134) months and for fish FPIES 13 (range 7–134) months. By 3 years of age, 67% of children with FPIES to milk and oat but none of the children with fish FPIES had developed tolerance. Allergic conditions like eczema and asthma were reported in 52% of the children. Conclusion: The cumulative FPIES incidence was 0.45% in 2016–2017. Most children presented with symptoms before 1 year of age, but the diagnosis was often delayed, especially for FPIES to fish. Tolerance development occurred at an earlier age when FPIES was triggered by milk and oat compared to fish. [ABSTRACT FROM AUTHOR]

Background: The microbiome associations of food protein‐induced enterocolitis syndrome (FPIES) are understudied. We sought to prospectively define the clinical features of FPIES in a birth cohort, and investigate for the evidence of gut dysbiosis. Methods: We identified children diagnosed with FPIES in the Gastrointestinal Microbiome and Allergic Proctocolitis Study, a healthy infant cohort. Children were assessed and stools were collected at each well child visit. The clinical features of the children with FPIES were summarized. Stool microbiome was analyzed using 16S rRNA sequencing comparing children with and without FPIES. Results: Of the 874 children followed up for 3 years, 8 FPIES cases (4 male) were identified, yielding a cumulative incidence of 0.92%. The most common triggers were oat and rice (n = 3, each) followed by milk (n = 2). The children with FPIES were more likely to have family history of food allergy (50% vs. 15.9% among unaffected, p =.03). The average age of disease presentation was 6 months old. During the first 6 months of life, stool from children with FPIES contained significantly less Bifidobacterium adolescentis, but more pathobionts, including Bacteroides spp. (especially Bacteroides fragilis), Holdemania spp., Lachnobacterium spp., and Acinetobacter lwoffii. The short‐chain fatty acid (SCFA)‐producing Bifidobacterium shunt was expressed significantly less in the stool from FPIES children. Conclusions: In this cohort, the cumulative incidence over the 3‐year study period was 0.92%. During the first 6 months of life, children with FPIES had evidence of dysbiosis and SCFA production pathway was expressed less in their stool, which may play an important role in the pathogenesis of FPIES. [ABSTRACT FROM AUTHOR]

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food-induced hypersensitivity disorder that occurs mostly in infants. Long considered a rare disease, a recent increase in physician awareness and publication of diagnosis of guidelines has resulted in an increase in recognized FPIES cases. We aimed to conduct a systematic review of FPIES studies in the past 10 years. A search was conducted on PubMed and Embase in March 2022. Our systematic review focused on 2 domains: (1) the most reported FPIES food triggers; and (2) the resolution rate and median age at resolution of patients with FPIES. We found that cow's milk was the most reported trigger globally. Patterns of the most common triggers varied by country, with fish being one of the most common triggers in the Mediterranean region. We also found that the rate and median age of resolution varied by trigger. Patients with FPIES to cow's milk acquired tolerance at a younger age (most by age 3 years), while fish-FPIES was more persistent (mean resolution by age 37 months–7 years). Overall, many studies found a resolution rate of 60% for any food. [ABSTRACT FROM AUTHOR]

We describe the case of a 1-year-old girl with food protein-induced enteropathy (FPE) that was difficult to diagnose. She was referred to our hospital with a 3-month history of diarrhea, vomiting, and weight loss. Although her diarrhea improved after a few days of fasting, oral intake of elemental diets, formula milk, or rice porridge resulted in repeated relapses. The serum IgE level was 1028 IU/mL, and radioallergosorbent tests were positive for milk, casein, alpha-lactalbumin, and other allergens. A histopathology of the duodenal mucosa revealed loss of mucosal villous structure, crypt hyperplasia, crypt apoptosis, and lymphocyte and eosinophil infiltration (

ABSTRACT Food protein‐induced enterocolitis syndrome (FPIES) is a non‐Immunoglobulin (non‐IgE)‐mediated food allergy. The elimination diet is the only therapy, the culprit food will be reintroduced if tolerance is acquired. However, it is possible that patients do not follow the recommendations given by the healthcare professional. We investigated if our advice to avoid the trigger food in patients with active FPIES and to reintroduce it in the diet in patients who achieved tolerance had been implemented. We interviewed by telephone the parents of children who were diagnosed with acute FPIES. About 23.2% of our patients disregarded our dietary recommendations: 6/42 (14.3%) of patients who passed a tolerance oral food challenge (OFC) did not eat the trigger food, 4/22 (18.2%) of patients who failed OFC ate the trigger food, and 9/18 (50.0%) of patients who did not perform a tolerance OFC ate the trigger food. We have analyzed some possible influencing factors and no difference was found to be statistically significant. Our results are in line with those reported for IgE‐mediated food allergies. As has already been proposed by others, we suggest reassessing food consumption in all patients after a food challenge.

Background: Mixed and non‐IgE‐mediated food allergy is a subset of immune‐mediated adverse food reactions that can impose a major burden on the quality of life of affected patients and their families. Clinical trials to study these diseases are reliant upon consistent and valid outcome measures that are relevant to both patients and clinicians, but the degree to which such stringent outcome reporting takes place is poorly studied. Objective: As part of the Core Outcome Measures for Food Allergy (COMFA) project, we identified outcomes reported in randomized clinical trials (RCT) of treatments for mixed or non‐IgE‐mediated food allergy. Design: In this systematic review, we searched the Ovid, MEDLINE and Embase databases for RCTs in children or adults investigating treatments for food protein‐induced enterocolitis syndrome, food protein‐induced allergic proctocolitis, food protein‐induced enteropathy and eosinophilic gastrointestinal disorders including eosinophilic esophagitis [EoE], eosinophilic gastritis and eosinophilic colitis published until 14 October 2022. Results: Twenty‐six eligible studies were identified, with 23 focused on EoE (88%). Most interventions were corticosteroids or monoclonal antibodies. All EoE studies assessed patient‐reported dysphagia, usually using a non‐validated questionnaire. Twenty‐two of 23 EoE studies used peak tissue eosinophil count as the primary outcome, usually using a non‐validated assessment method, and other immunological markers were only exploratory. Thirteen (57%) EoE studies reported endoscopic outcomes of which six used a validated scoring tool recently recommended as a core outcome for EoE trials. Funding source was not obviously associated with likelihood of an RCT reporting mechanistic versus patient‐reported outcomes. Only 3 (12%) RCTs concerned forms of food allergy other than EoE, and they reported on fecal immunological markers and patient‐reported outcomes. Conclusions: Outcomes measured in clinical trials of EoE and non‐IgE‐mediated food allergy are heterogeneous and largely non‐validated. Core outcomes for EoE have been developed and need to be used in future trials. For other forms of mixed or non‐IgE‐mediated food allergies, core outcome development is needed to support the development of effective treatments. Systematic review registration: OSF public registry DOI:10.17605/OSF.IO/AZX8S [ABSTRACT FROM AUTHOR]

Objective: Food protein-induced enterocolitis syndrome (FPIES) is an uncommon, non-IgE (immunoglobulin E) -mediated food allergy that mainly affects infants and young children. Our study aims to evaluate the etiology, clinical phenotypes, and tolerance status of our cases with FPIES. Method: The file records of the patients who were followed up with the diagnosis of FPIES in the Departments of Pediatric Allergy and Gastroenterology of our hospital, between September 2016 and June 2022 were examined, and families who could not attend follow-up visits regularly were contacted by phone. Results: Twelve (66.66%) of 18 cases with a mean age of admission of 33.0±27.5 (2-108) months were boy. The triggers of FPIES were fish in 66.66%, cow’s milk in 16.66%, eggs in 5.55%, eggs and milk in 5.55%, and potato in 5.55% of the patients. While 94.44% of the cases had acute FPIES, and 44.4% of them had early-onset (<9 months) FPIES. The most common symptoms were vomiting (100%), diarrhea (38.88%), pallor (27.77%), lethargy (22.22%). Food-specific IgE sensitization was found in 5.55% of the patients, while tolerance developed in 33.33% of the cases during the follow-up. The mean age of tolerance development was 63±42 (19-112) months. Conclusion: It is important to have knowledge about the symptoms of FPIES for accurate and early diagnosis. While cow’s milk is the most prevalent triggers of FPIES in the literature, fish was at the forefront in our series. Despite the limited number of cases, our results are important in terms of giving us an idea about the triggers of FPIES in the western regions of Turkey. [ABSTRACT FROM AUTHOR]

All patients were not sensitized to -5-gliadin; however, one patient had a slightly elevated wheat-sIgE level of 0.42 kU SB A sb /L. 1 TABLE Characteristics of the seven patients with wheat-induced FPIES. The proportion of patients who became tolerant to wheat increased with age, and at the age of 5 years, six (86%) patients were confirmed to have achieved tolerance and the remaining patient was able to consume 52 mg of wheat protein (Figure 2). Patients who either met the diagnosis criteria based on their history of symptoms or symptoms exhibited during OFC were defined as wheat-FPIES patients. Keywords: food protein-induced enterocolitis syndrome; prognosis; tolerance; wheat EN food protein-induced enterocolitis syndrome prognosis tolerance wheat 1 4 4 03/30/23 20230301 NES 230301 Key message The rate of tolerance acquisition in infants with food protein-induced enterocolitis syndrome caused by wheat increased with age and resolved in most patients by the age of 5 years. [Extracted from the article]

This article discusses the prognosis and remission patterns of solid food protein-induced enterocolitis syndrome (FPIES) in children. FPIES is a non-immunoglobulin E (IgE) mediated food allergy that typically occurs in children after the introduction of complementary foods. The study found that most FPIES patients achieve tolerance with age, but the management of determining tolerance to causative foods is still uncertain. The leading cause of solid FPIES in the study was egg yolk, which may be attributed to the Japanese recommendation of early introduction of egg yolk to infants. The study suggests that timely evaluation of tolerance acquisition is crucial to avoid unnecessary elimination in solid FPIES patients, particularly in cases of egg yolk and wheat FPIES. [Extracted from the article]

Reports of food protein–induced enterocolitis syndrome (FPIES) in Japan have been increasing. However, the disease itself and the treatment options are poorly understood by both patients and medical professionals. The objective of this study is to develop an action plan for acute FPIES in Japan. We prepared a single–sheet action plan that describes the management of acute FPIES episodes for caregivers on one side and medical professionals on the reverse side. To evaluate the content of the action plan, we distributed a questionnaire to caregivers of patients with FPIES and to physicians who would encounter patients with FPIES. Changes to the FPIES action plan were made based on the feedback from the participants. The Delphi method was utilized to finalize the action plan. The participants of the initial survey found the action plan to be useful but the process for determining severity to be impractical. After discussion, the authors made appropriate improvements. By the Delphi method, consensus was reached on the revised FPIES action plan. In conclusion, this Japanese FPIES action plan was created by physicians from multiple subspecialties and caregivers of patients with FPIES. The action plan may improve the management of acute FPIES reactions in the Japanese community.

We report the case of a 4-year-old child who presented with vomiting, abdominal pain, and intense pallor 2 h after amoxicillin ingestion. An IgE-mediated reaction was suspected at first, which was finally diagnosed as a drug-induced enterocolitis syndrome. In this rare and poorly described non-IgE-mediated drug allergy, adrenaline is not effective. This diagnostic challenge must be known in order to administer adequate treatment, i.e., antiemetic drugs (ondansetron) and fluid challenge. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to clarify the clinical characteristics and management of infants with suspected acute food protein–induced enterocolitis syndrome (FPIES) who presented to the pediatric emergency department (ED) before and after the guidelines were published. Methods: This was a retrospective cohort study. We classified the infants as "acute FPIES‐like symptoms" who were younger than 12 months of age and visited the pediatric ED of the National Center for Child Health and Development due to vomiting 1–4 h after food ingestion without any causative disease, such as infection. The medical records of those infants in 2015 and 2021 were reviewed. We used the nonparametric Mann–Whitney U test to compare two groups for continuous variables, whereas chi‐squared or Fisher's exact tests were used for nominal variables. Results: The number of infants with acute FPIES‐like symptoms was 15 (13%) in 2015 and 14 (15%) in 2021. The trigger foods were cow's milk or dairy products in half of the infants, and five as a result of ingestion of hen's eggs in 2021, compared to zero cases in 2015. Five in 2015 and 12 in 2021 required examination at the ED. Three in 2015 and six in 2021 met the diagnostic criteria for acute FPIES in the international consensus guidelines. The emergency physicians did not record at least four minor criteria for acute FPIES in seven in 2015 and five in 2021. No infants (0%) in 2015 and two (14%) in 2021 were referred to the allergy department by an emergency physician. Conclusions: Acute FPIES should be considered one of the differential diagnoses of vomiting, and pediatric medical staff should be aware of FPIES diagnostic criteria and appropriately refer suspected cases to a specialist. [ABSTRACT FROM AUTHOR]

Food protein–induced enterocolitis syndrome (FPIES) was first described in detail in the late 20th century as a non–IgE-mediated food allergy characterized by delayed gastrointestinal symptoms after ingestion of a trigger food. Although the initial case series reported infants reacting to cow's milk– and soy-based formulas, we now recognize that FPIES affects patients across the age spectrum. This brief review highlights our evolving understanding of FPIES with a discussion of triggers, epidemiology, food challenges, and pathophysiology. [ABSTRACT FROM AUTHOR]

Food protein-induced enterocolitis syndrome （FPIES） is a critical non-IgE-mediated food allergy,occurs mostly in infants. Dehydration shock may occur in severe FPIES cases upon acute onset, and growth retardation probably occurs in patients with chronic FPIES. In 2017, Adverse Reactions to Foods Committee, American College of Allergy, Asthma and Immunology and International FPIES Association jointly formulated and released International Consensus Guidelines for Diagnosis and Treatment of Food Protein-induced Enterocolitis Syndrome, which is the only diagnosis and treatment guidelines for FPIES. Based on literature review and clinical evidence, this guideline proposes 30 statements, which provide reference for clinical diagnosis and treatment of FPIES. At present, medical staff has a low awareness rate of FPIES, and relevant studies are still lacking in China. In this article, clinical manifestations, diagnosis, auxiliary examination, treatment and prognosis of FPIES were explicitly interpreted, aiming to deepen the understanding of FPIES and improve the diagnosis and treatment levels among Chinese medical staff.

Abstract Background Food Protein-Induced Enterocolitis Syndrome (FPIES) is a non-IgE mediated food allergy most commonly presenting in infants. The most common food triggers include soy, cow’s milk and grains. Symptoms may include intractable vomiting, diarrhea, lethargy, pallor, abdominal distention, hypotension and/or shock. Oral food challenges (OFCs) given at food protein dose of 0.06–0.6 g/kg in 3 equivalent doses administered over a few hours are recommended in guidelines to confirm a diagnosis. Case presentation The patient is a 6-month-old girl with a history of severe FPIES symptoms to egg. In our clinic, we perform OFC with 1/100 serving dose on visit 1 and then increase the dose monthly. The patient takes the tolerated dose daily at home between visits. An OFC to baked egg at 1/100 of a serving was performed and was well-tolerated on her initial visit. The patient remained on the same dose upon returning home. Within 1-week, she developed FPIES symptoms including watery diarrhea and severe emesis requiring ondansetron. She required an Emergency Department visit for one of the reactions. Conclusions Our patient had severe FPIES symptoms with a small amount of egg. We believe that administration of three large food challenge doses on one clinic visit, as guidelines currently suggest, does not allow adequate time for symptoms to appear. Our patient likely would have suffered a severe reaction. Also, this guidelines protocol does not allow for monitoring of more delayed or chronic FPIES. We propose a modified protocol to OFCs with cautious up-dosing to allow for safer OFCs and monitoring of chronic FPIES. We have implemented an OFC approach where only one food challenge dose (starting with 1/100 of final dose) is given at each visit. The up-titration of the dose is completed every 4-weeks with one dose only. When the serving sized dose is reached and tolerated, the food can be maintained in the diet.

Shouling Zhang, Scott Sicherer, M Cecilia Berin, Amanda Agyemang Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, Kravis Children’s Hospital, The Elliot and Roslyn Jaffe Food Allergy Institute, New York, NY, USACorrespondence: Amanda AgyemangDepartment of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, Kravis Children’s Hospital, The Elliot and Roslyn Jaffe Food Allergy Institute, One Gustave L. Levy Place, Box 1198, New York, NY, 10029, USATel +212 241-5548Email amanda.agyemang@mountsinai.orgAbstract: Non-IgE-mediated food allergies are a group of disorders characterized by subacute or chronic inflammatory processes in the gut. Unlike IgE mediated food allergies that may result in multi-organ system anaphylaxis, the non-IgE mediated food allergies primarily affect the gastrointestinal tract. This review outlines the clinical manifestations, epidemiology, pathophysiology, and management of non-IgE-mediated food allergies. An updated literature search of selected non-IgE-mediated food allergies was conducted for this review using PubMed database to the current year (2021). Reviewed disorders include food protein-induced enterocolitis syndrome (FPIES), food-protein enteropathy (FPE), food protein-induced allergic proctocolitis (FPIAP), and eosinophilic gastrointestinal disorders (EGIDs) such as eosinophilic esophagitis (EoE). While extensive gains have been made in understanding FPIES, FPIAP, FPE, and EoE, more information is needed on the pathophysiology of these food allergies. Similarities among them include involvement of innate immunity, T-lymphocyte processes, alteration of the intestinal lumen at the cellular level with the appearance of inflammatory cells and associated histologic changes, and specific cytokine profiles suggesting food-specific, T-cell, and immune-mediated responses. While FPIES and FPIAP typically resolve in early childhood, EGIDs typically do not. Emerging new therapies for EoE offer promise of additional treatment options. Further studies identifying the immunopathogenesis, associated biomarkers, and mechanisms of tolerance are needed to inform prevention, diagnosis and management.Keywords: food protein-induced enterocolitis syndrome, FPIES, food protein-induced enteropathy, FPE, food protein-induced allergic proctocolitis, FPIAP, eosinophilic gastrointestinal disorders, EGIDs, eosinophilic esophagitis, EoE, pathophysiology

A 1‐month‐old male, exclusively breastfed, presented with 24 h of bloody stools, vomiting, metabolic acidosis, and pneumatosis intestinalis. The patient was initially treated for necrotizing enterocolitis (NEC). However, after suspecting food protein‐induced enterocolitis syndrome (FPIES), oral feeding was resumed using an exclusive elemental formula, and the biochemical and radiological findings were resolved. [ABSTRACT FROM AUTHOR]

Purpose of Review: Food protein–induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by delayed, and potentially severe, gastrointestinal symptoms. Since the advent of a specific diagnostic code and establishment of diagnostic guidelines, our understanding of this condition has grown. Recent Findings: FPIES affects patients from early infancy into adulthood. Any food can be a trigger, and common culprit foods vary geographically and by age. An understanding of the complex underlying immune mechanisms remains elusive, although studies show pan-leukocyte activation, cytokine release, and increased gastrointestinal permeability. Management involves trigger avoidance, and patients may benefit from the support of a dietitian to ensure adequate nutrient intake. Tolerance develops over time for most children, but due to the risk of severe symptoms, re-introduction of a suspected FPIES trigger is recommended only under supervision at an oral food challenge. Studies continue to evaluate the optimal challenge protocol. Caregivers of children with FPIES report high levels of anxiety and stress, which is attributed to the dramatic symptomatology, dietary restrictions, nutritional concerns, lack of confirmatory diagnostic tests, and limited tools for management of reactions. Summary: Our understanding of the FPIES diagnosis has improved over the last few decades, but there remain opportunities, particularly regarding discerning the pathophysiology and best management practices. [ABSTRACT FROM AUTHOR]

We describe the case of a 1-year-old girl with food protein-induced enteropathy (FPE) that was difficult to diagnose. She was referred to our hospital with a 3-month history of diarrhea, vomiting, and weight loss. Although her diarrhea improved after a few days of fasting, oral intake of elemental diets, formula milk, or rice porridge resulted in repeated relapses. The serum IgE level was 1028 IU/mL, and radioallergosorbent tests were positive for milk, casein, alpha-lactalbumin, and other allergens. A histopathology of the duodenal mucosa revealed loss of mucosal villous structure, crypt hyperplasia, crypt apoptosis, and lymphocyte and eosinophil infiltration (<20 eos/hpf) into the lamina propria. After prednisolone (PSL) therapy and the complete removal of cows' milk and chicken eggs from her diet, the patient's diarrhea disappeared. Five months after discontinuing oral PSL and complete removal of cows' milk and chicken eggs, the duodenum exhibited normal mucosal villous structure and well-differentiated ducts. No abnormalities were observed in the egg rechallenge; however, diarrhea recurred after the cows' milk rechallenge. Thus, histopathologic examination of the gastrointestinal mucosa is useful for diagnosing FPE similar to oral food challenges, and re-evaluation after elimination diet therapy may be beneficial to rule out other diseases. [ABSTRACT FROM AUTHOR]

Introduction: We previously reported that thymus and activation-regulated chemokine (TARC) levels measured after vomiting are useful predictors of a food protein-induced enterocolitis syndrome (FPIES) diagnosis. However, interpreting TARC levels in patients with eczema is difficult, as the levels are similarly elevated in patients with eczema caused by atopic dermatitis (AD). Therefore, we aimed to investigate whether it is possible to predict whether FPIES or AD is responsible for elevated TARC levels by simultaneously measuring TARC and squamous cell carcinoma antigen 2 (SCCA2), another T-helper type 2 biomarker. Methods: Twenty-one episodes in 11 patients with FPIES (FPIES group) and 42 age-matched patients with AD (AD group) were included in this study. Serum TARC and SCCA2 levels were measured, and those values and relative ratios were compared between groups. Results: The median age was 1.1 years in the FPIES group and 1.6 years in the AD group (p = 0.492). The median (interquartile range [IQR]) serum TARC concentration was significantly higher in the FPIES group than in the AD group (2,486 [1,815–4,097] pg/mL and 1,451 [1,201–1,751] pg/mL, respectively; p = 0.002). The median (IQR) SCCA2 concentration was significantly higher in the AD group than in the FPIES group (1.9 [1.3–2.9] pg/mL and 0.8 [0.6–1.5] pg/mL, respectively; p < 0.001). After matching, the analysis using stratified TARC values revealed no significant difference in TARC values between the FPIES and AD groups; however, the TARC/SCCA2 ratio was significantly higher in the FPIES group. Conclusion: Assessing the relative TARC/SCCA2 ratio may help predict whether elevated TARC levels measured after vomiting are caused by FPIES or AD. [ABSTRACT FROM AUTHOR]

Background: Several recent studies have reported egg yolk-associated food protein-induced enterocolitis syndrome (FPIES) in Japan. We previously reported the usefulness of post-emetic thymus and activation-regulated chemokine (TARC) levels for the diagnosis and evaluation of symptom severity in FPIES caused by solid foods including egg yolk. However, there are no studies on the usefulness of TARC as a prognostic biomarker. Objective: The aim of the study was to evaluate the post-emetic TARC levels, clinical symptoms, and post-index event results of the egg yolk oral food challenge test (OFC), and retrospectively investigate predictive factors of the subsequent OFC result. Method: This retrospective study included 12 patients with egg yolk FPIES. The following long-term management protocol for egg yolk FPIES was mandatory for study inclusion: Patients visited the emergency department, met the diagnostic criteria of FPIES, and underwent an egg yolk OFC 6–12 months after complete elimination of egg yolk. If the result of the OFC was positive, the patient underwent the OFC every year until it was negative. We analyzed a total of 20 episodes (12 department visits and eight positive OFCs). The blood test data, including post-emetic TARC level and symptom severity, were compared between the next-OFC-positive group and the next-OFC-negative group. In addition, tolerance development over follow-up was analyzed. Results: The median (range) ages of the next-OFC-positive and negative groups were 11 (6–33) and 10 (7–21) months, respectively. The median (range) serum TARC (pg/mL) level was 5,208 (2,009–8,147) in the next-OFC-positive group, which was significantly higher (p = 0.004) than that in the next-OFC-negative group, which was 1,803 (905–3,754). There were no significant differences in other hematological results. The next-OFC-positive group had greater severity compared to the next-OFC-negative group (p = 0.026). The remission rate was approximately 30% at 24 months and 80% at 36 months. Conclusion: Post-emetic TARC levels may predict the short-term prognosis of egg yolk FPIES after approximately 1 year and could be useful for the management of egg yolk FPIES. [ABSTRACT FROM AUTHOR]

Introduction: Patients with food protein-induced enterocolitis syndrome (FPIES) have elevated thymus and activation-regulated chemokine (TARC) levels in the acute phase. However, to the best of our knowledge, no study has evaluated TARC levels in the acute phase of immunoglobulin E-dependent food allergy (IgE-FA). If TARC elevation is a specific response to FPIES among FAs, TARC measurement may help distinguish between FPIES and IgE-FA. Thus, we investigated acute phase TARC levels in patients with FPIES and IgE-FA. Methods: Thirty-one episodes in 16 patients with FPIES and 20 episodes (13 were anaphylaxis) in 20 patients with IgE-FA were included. Patients with eczema were excluded. Serum TARC levels within 6 h of allergic reaction onset and age-adjusted TARC ratios (TARC levels divided by age-specific normal TARC values) were compared between the groups. Results: The median age was 1.1 and 3.6 years in the FPIES and IgE-FA groups, respectively (P < 0.001). The median (range) serum TARC (pg/mL) levels were significantly higher in the FPIES group than in the IgE-FA group [1,283 (410–3,821) versus 377 (109–1,539); P < 0.001]. The median (range) age-adjusted TARC ratios were also significantly higher in the FPIES group [2.56 (0.57–7.86) versus 1.08 (0.15–2.17); P < 0.001]. The area under the curve (AUC) for TARC to distinguish FPIES from IgE-FA was 0.926, and the AUC for the age-adjusted TARC ratio was 0.850. The odds ratio for FPIES diagnosis per 1,000 pg/mL increase in TARC was 31.6 (P = 0.002), and the odds ratio adjusted by age was 17.1 (P = 0.016). Conclusion: Acute phase TARC levels were higher in patients with FPIES than in patients with IgE-FA. The increase in acute phase TARC levels was considered to be a specific response to FPIES among FAs. Measurement of TARC levels in the acute phase may help differentiate FPIES from IgE-FA. [ABSTRACT FROM AUTHOR]

Food protein‐induced enterocolitis syndrome (FPIES) is a non‐Immunoglobulin (non‐IgE)‐mediated food allergy. The elimination diet is the only therapy, the culprit food will be reintroduced if tolerance is acquired. However, it is possible that patients do not follow the recommendations given by the healthcare professional. We investigated if our advice to avoid the trigger food in patients with active FPIES and to reintroduce it in the diet in patients who achieved tolerance had been implemented. We interviewed by telephone the parents of children who were diagnosed with acute FPIES. About 23.2% of our patients disregarded our dietary recommendations: 6/42 (14.3%) of patients who passed a tolerance oral food challenge (OFC) did not eat the trigger food, 4/22 (18.2%) of patients who failed OFC ate the trigger food, and 9/18 (50.0%) of patients who did not perform a tolerance OFC ate the trigger food. We have analyzed some possible influencing factors and no difference was found to be statistically significant. Our results are in line with those reported for IgE‐mediated food allergies. As has already been proposed by others, we suggest reassessing food consumption in all patients after a food challenge. [ABSTRACT FROM AUTHOR]

Abstract A 1‐month‐old male, exclusively breastfed, presented with 24 h of bloody stools, vomiting, metabolic acidosis, and pneumatosis intestinalis. The patient was initially treated for necrotizing enterocolitis (NEC). However, after suspecting food protein‐induced enterocolitis syndrome (FPIES), oral feeding was resumed using an exclusive elemental formula, and the biochemical and radiological findings were resolved.

Introduction: Food protein-induced enterocolitis syndrome (FPIES) is a rare non-IgE, cell-mediated food allergy disorder. We aimed to report the demographic characteristics, clinical features, and management of pediatric patients with FPIES. Methods: This retrospective study included all children diagnosed with FPIES at the pediatric allergy departments of the participating twelve study centers from January 2015 to November 2020. Results: A total of 73 patients (39 males, 53.4%) with a male/female ratio of 1.1 were included in the study. The median (interquartile ranges) age at symptom onset was 6 months (0.5–168, 4–9.5). The most frequent offending foods were cow's milk, egg's yolk, fish, and egg's white, identified in 38.4% (n = 28), 32.9% (n = 24), 21.9% (n = 16) and 20.5% (n = 15) of the patients, respectively. The total number of reported FPIES episodes was 290 (3.9 episodes per child). Oral food challenge (OFC) was performed in 54.8% (n = 40) of the patients, and tolerance was detected in 17 OFCs (42.5%) at a median age of 15 months (range 8–132 months). Conclusion: FPIES is a non-IgE-mediated food hypersensitivity that commonly affects infants and is often misdiagnosed. The pathophysiology of the disease remains unclear and the low awareness of FPIES among physicians and parents highlights the need for more education. [ABSTRACT FROM AUTHOR]

Down syndrome (DS) is one of the most common chromosomal anomalies. Gastrointestinal disorders in DS are predominantly related to anatomical anomalies and celiac disease. In 2015, the first two cases of non-IgE-mediated food allergy in patients with DS were described. However, gastrointestinal symptoms experienced by subjects with DS have never been related to a possible non-IgE-mediated food allergy and a Food Protein-induced Enterocolitis syndrome (FPIES). A retrospective descriptive single-center study was conducted. Subjects included were children with acute FPIES who entered our institutional follow-up protocol between January 2013 and January 2020. Among the 85 patients (forty-nine boys—57.6%), ten (11.76%) were children with DS. In our population, the FPIES triggers included different foods (such as milk, egg, fruit, fish, wheat, soy, beef, etc.). Nine patients with DS showed FPIES reactions after ingesting cow's milk (one even with beef and three with soy), while the last one was affected by FPIES to fish. Considering the subgroup of patients affected by cow's milk FPIES (40 subjects overall), 22.5% had a diagnosis of DS. Patients with DS experienced acute FPIES reactions with a severity degree slightly higher than that reported in other patients, ranging from mild-moderate to severe or very severe. During the acute reactions, the patients with DS showed increased white blood cell production, absolute neutrophil count and C-reactive protein levels. This series provides a starting point for novel hypothesis-testing clinical research and possible specific immunological alterations in FPIES children with or without DS. [ABSTRACT FROM AUTHOR]

Le syndrome d'entérocolite induite par les protéines alimentaires (SEIPA) est une allergie alimentaire non IgE-médiée, souvent sous-diagnostiquée malgré une prévalence croissante. Cette étude vise à évaluer l'impact du SEIPA sur la qualité de vie et à identifier les facteurs de risque de souffrance psychosociale. Nous avons collecté les données d'une cohorte de 48 patients pédiatriques atteints de SEIPA, (recrutés par des allergologues libéraux et hospitaliers) via des entretiens téléphoniques auprès des familles. La qualité de vie, évaluée à travers les questionnaires QUALIN et Peds QL, est généralement préservée, mais les aspects psychopathologiques et la sociabilité sont altérés. Les inquiétudes des parents sont significatives, avec 61 % ressentant de l'anxiété pendant la période de diversification alimentaire. Concernant le bien-être émotionnel, 85 % des parents expriment des préoccupations, tandis que le SEIPA génère du stress chez 75 % d'entre eux. Les limitations d'activités familiales touchent 62 % des familles. Le SEIPA a un impact sur la vie sociale des enfants (54 %) et un impact financier important pour 57 % des familles. On retrouve une influence négative sur la qualité de vie des antécédents d'hospitalisation, du nombre de consultations aux urgences pour SEIPA, du lait de vache comme aliment déclencheur et du SEIPA à de multiples aliments. Ces résultats soulignent l'importance de considérer les dimensions psychosociales dans la prise en charge globale du SEIPA. The food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy, often underdiagnosed despite an increasing prevalence. This study aims to assess the impact of FPIES on the quality of life and identify risk factors for psychosocial distress. We collected data from a cohort of 48 pediatric patients with FPIES, recruited by private and hospital allergists through telephone interviews with families. Quality of life, assessed through QUALIN and Peds QL questionnaires, is generally preserved, but psychopathological aspects and sociability are affected. Parental concerns are significant, with 61% experiencing anxiety during the food diversification period. Regarding emotional well-being, 85% of parents express concerns, while FPIES induces stress in 75% of them. Family activity limitations affect 62% of families. FPIES impacts the social life of children (54%) and has a significant financial impact on 57% of families. Negative influences on quality of life include a history of hospitalization, the number of emergency room visits for FPIES, cow's milk as a triggering food, and FPIES to multiple foods. These results emphasize the importance of considering psychosocial dimensions in the overall management of FPIES. [ABSTRACT FROM AUTHOR]

Early diagnosis, food hypersensitivity, egg yolk, food protein-induced enterocolitis syndrome, FPIES, tolerance acquisition Keywords: early diagnosis; egg yolk; food hypersensitivity; food protein-induced enterocolitis syndrome; FPIES; tolerance acquisition EN early diagnosis egg yolk food hypersensitivity food protein-induced enterocolitis syndrome FPIES tolerance acquisition 1 4 4 04/28/22 20220401 NES 220401 ACKNOWLEDGMENTS We thank all patients who participated in this study. Early diagnosis of egg yolk-associated FPIES relates to early tolerance acquisition. [Extracted from the article]

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE, cell-mediated food allergy, commonly diagnosed in infants and young children. In recent years, new-onset adult FPIES has been recognized. The underlying pathogenic mechanism of FPIES has yet to be elucidated, thus disease-specific diagnostic biomarkers have yet to be determined and an oral food challenge (OFC) remains the gold-standard for the diagnosis. Pediatric patients with FPIES classically present with symptoms of delayed, repetitive vomiting approximately 1 to 4 hours following ingestion of a food allergen. However, adults with FPIES have been reported to have a different symptom profile and different food triggers compared to the pediatric FPIES population. The current FPIES diagnostic criteria may not be appropriate for the diagnosis of adult FPIES patients, thus an oral food challenge remains a diagnostic tool. This review provides an overview of the current literature on the clinical presentation, epidemiology, diagnosis, triggers and management of adult FPIES.

To explore the value of abdominal ultrasound in the differential diagnosis of neonatal food protein-induced enterocolitis syndrome (NFPIES) and early neonatal necrotic enterocolitis (NEC). Methods Twenty-one children diagnosed as NFPIES and early NEC (n=48) were selected in this study. Data of sex, gestational age, clinical symptoms (vomiting, abdominal distension and bloody stool) and the percentage of blood eosinophils (EO) within 8 hours of clinical symptoms were collected. The time of the first abdominal ultrasound examination of all children was within 8 hours of the occurrence of clinical symptoms, and the interval between the abdominal ultrasound examination and the first examination was 8-24 hours. The changes of abdominal ultrasound signs (intestinal wall pneumatosis, intestinal peristalsis, intestinal wall thickening and peritoneal effusion) were dynamically compared. Results There were no significant differences in general baseline data between the NFPIES group and the early NEC group. The proportion of peripheral blood EO and the proportion of children with EO ratio≥0.05 were significantly higher in the NFPIES group than those in the early NEC group (P＜0.01). The proportion of children with positive abdominal ultrasound signs was lower in the NFPIES group than that in the early NEC group (P＜0.05). The ultrasonographic signs of peristalsis showed slowing at the diseased site, and the remaining peristalsis was normal without peristalsis disappearance or peritoneal effusion. In the re-examination of abdominal ultrasound, the ultrasound signs of gas in the intestinal wall and slowing of bowel movement were significantly lower in the NFPIES group than those with positive abdominal ultrasound examination for the first time (P＜0.05), while there was no significant difference in the proportion of four children with positive abdominal ultrasound signs in the early NEC group compared with the first examination. In the re-examination of abdominal ultrasound, the proportion of four children with positive ultrasound signs was lower in the NFPIES group than that in the early NEC group (P＜0.01). [ABSTRACT FROM AUTHOR]

Background: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a non-IgE mediated food allergy most commonly presenting in infants. The most common food triggers include soy, cow's milk and grains. Symptoms may include intractable vomiting, diarrhea, lethargy, pallor, abdominal distention, hypotension and/or shock. Oral food challenges (OFCs) given at food protein dose of 0.06–0.6 g/kg in 3 equivalent doses administered over a few hours are recommended in guidelines to confirm a diagnosis. Case presentation: The patient is a 6-month-old girl with a history of severe FPIES symptoms to egg. In our clinic, we perform OFC with 1/100 serving dose on visit 1 and then increase the dose monthly. The patient takes the tolerated dose daily at home between visits. An OFC to baked egg at 1/100 of a serving was performed and was well-tolerated on her initial visit. The patient remained on the same dose upon returning home. Within 1-week, she developed FPIES symptoms including watery diarrhea and severe emesis requiring ondansetron. She required an Emergency Department visit for one of the reactions. Conclusions: Our patient had severe FPIES symptoms with a small amount of egg. We believe that administration of three large food challenge doses on one clinic visit, as guidelines currently suggest, does not allow adequate time for symptoms to appear. Our patient likely would have suffered a severe reaction. Also, this guidelines protocol does not allow for monitoring of more delayed or chronic FPIES. We propose a modified protocol to OFCs with cautious up-dosing to allow for safer OFCs and monitoring of chronic FPIES. We have implemented an OFC approach where only one food challenge dose (starting with 1/100 of final dose) is given at each visit. The up-titration of the dose is completed every 4-weeks with one dose only. When the serving sized dose is reached and tolerated, the food can be maintained in the diet. [ABSTRACT FROM AUTHOR]

The diagnosis of drug‐induced enterocolitis syndrome (DIES), resembling the typical findings of a well‐known disease, the food protein‐induced enterocolitis syndrome (FPIES), was acknowledged in the first publication on the topic in 2014. Ten cases of DIES have been described so far. Unanswered questions concerning DIES include its pathogenetic mechanism, natural history, the possible presence of predisposing genetic factors, and the potential existence of its atypical forms. DIES is a recently defined and intriguing clinical entity, similar to FPIES but triggered by drugs. It seems well‐defined from the clinical point of view, but its pathogenetic mechanisms are not known. DIES deserves more attention among allergists, especially among the professionals who work with children, and all efforts should be conceived to improve its correct recognition and accurate management. [ABSTRACT FROM AUTHOR]

Keywords: atypical; differential diagnosis; food protein-induced enterocolitis syndrome; low birthweight; necrotizing enterocolitis; preterm newborns; twins EN atypical differential diagnosis food protein-induced enterocolitis syndrome low birthweight necrotizing enterocolitis preterm newborns twins 1 5 5 01/05/22 20220101 NES 220101 CONFLICT OF INTEREST The authors declare that there are no conflicts of interest. In preterm newborns, acute FPIES should be carefully differentiated, in particular, from necrotizing enterocolitis (NEC). In some cases, this finding, which is not typical in FPIES, along with leukocytosis with neutrophilia and thrombocytosis could be an important tool to differentiate between NEC and FPIES in preterm newborns. FPIES was not suspected initially in any of the patients, but other medical and surgical conditions have been hypothesized; in the suspicion of NEC, empiric broad-spectrum parenteral antibiotic therapy was started in three out of six patients (see Table 2 for details). [Extracted from the article]

Keywords: Food protein-induced enterocolitis syndrome; FPIES; Thymus and activation-regulated chemokine EN Food protein-induced enterocolitis syndrome FPIES Thymus and activation-regulated chemokine 1 4 4 01/05/22 20220101 NES 220101 ACKNOWLEDGMENT We thank all patients who participated in this study. A recent report has demonstrated that serum levels of TARC elevate after oral food challenge (OFC) in two patients with FPIES, suggesting that serum TARC levels are potential biomarker of the disease.3 We defined TARC ratio as the ratio of post-OFC to pre-OFC TARC levels. To validate the utility of TARC in the diagnosis of FPIES, we examined TARC ratio in a larger number of patients with FPIES. In contrast to OFC-positive patients, TARC levels showed no changes in any OFC-negative patients who finally achieved tolerances of solid FPIES. [Extracted from the article]

Abstract Background Food Protein-Induced Enterocolitis Syndrome (FPIES) is a non IgE-mediated food allergy that generally affects children in the first year of life. Usually symptoms break out when formula milk or solid foods are introduced for the first time but they might also appear in exclusively breastfed infants, since the trigger elements, especially cow’s milk proteins, can be conveyed by maternal milk as well. FPIES in exclusively breastfed babies is a very rare clinical condition and only few cases have been reported in the medical literature. Case presentation We describe two cases of FPIES in exclusively breastfed babies. The first one is a two-month-old infant with a brief history of vomit and diarrhea that presented to the Emergency Department in septic-like conditions. The main laboratory finding was a significant increase in methemoglobin (13%). Clinically, we noted that, when breastfeeding was suspended, diarrhea drastically improved, and vice versa when maternal milk was reintroduced. An amino acid-based formula allowed a complete normalization of the symptoms. The second one is a three-month-old infant admitted for a 3 days history of persistent vomit and diarrhea. Blood tests showed a raised level of methemoglobin (7%). An esophagogastroduodenoscopy was performed and biopsies showed an eosinophilic infiltration of the duodenal mucosa. A maternal exclusion diet and an amino acid-based formula allowed a rapid regularization of the bowel function. Conclusions We searched all the cases of FPIES in exclusively breastfed babies reported in the medical literature, identifying eight patients, with an average age of 3 months (range 15 days – 6 months). The majority of the cases were initially diagnosed as gastroenteritis or sepsis, five cases were characterized by an acute on chronic scenario and cow’s milk was the most frequently involved food. Methemoglobin was never tested. An oral food challenge test was performed in two patients. FPIES in exclusively breastfed infants is a rare condition that, in the presence of compatible history and symptoms, should be considered also in exclusively breastfed babies. The evaluation of methemoglobin can simplify the diagnostic process.

Introduction: Food protein-induced enterocolitis is a non-immunoglobulin E-mediated food allergy with acute manifestations like recurrent vomiting, dehydration, and shock. It is a rare pathology that requires a high index of suspicion. Pseudo-Bartter syndrome (metabolic alkalosis, hypokalemia and hypochloremia in the absence of tubulopathy) is an infrequent complication of cystic fibrosis. Case report: A 5-month-old boy with recurrent vomiting, dehydration, and shock; who had been breastfed and had consumed baby formula three hours prior to the onset of symptoms. Laboratory tests confirmed hyponatremia, hypochloremic metabolic alkalosis, and hypokalemia **in absence of tubulopathy; two iontophoresis showed altered results, stool elastase was decreased, and genetic sequencing confirmed the diagnosis of cystic fibrosis. The provocation test confirmed food protein-induced enterocolitis syndrome. Conclusion: Recurrent vomiting and dehydration after the intake of milk formula must lead to suspicion of food protein-induced enterocolitis syndrome. If pseudo-Bartter syndrome is found, cystic fibrosis must be ruled out. [ABSTRACT FROM AUTHOR]