The immune mechanism and potential biomarkers of non-IgE-mediated food allergy / 中华实用儿科临床杂志

The immune mechanism of non-IgE-mediated food allergy is quite complex.Due to the lack of specific laboratory indicators and limited diagnosis and treatment methods, non-IgE-mediated food allergy is usually misdiagnosed.Therefore, it is urgent to clarify the pathogenesis of the disease and search for specific biomarkers and novel therapeutic targets.This review aims to summarize current research results on the immune mechanism of non-IgE-mediated food allergy from two aspects, including the specific immunity and innate immunity, and to explore the potential diagnostic markers.The results may provide novel ideas for effective therapeutic strategies of non-IgE-mediated food allergy.

Food protein-induced enterocolitis syndrome: a clinical analysis of 5 cases and literature review / 中华实用儿科临床杂志

Objective:To summarize and analyze the clinical features of food protein-induced enterocolitis syndrome (FPIES).Methods:The medical history and follow-up data of 5 children with FPIES diagnosed in Department of Gastroenterology, Beijing Children′s Hospital of Capital Medical University from July 2018 to September 2019 were collected, and their clinical characteristics were summarized and analyzed.Results:Five children with FPIES were all infants, including 3 females and 2 males.Before the onset of the disease, the cases visited multiple departments and the average number of visits before diagnosis was 3.There were 4 cases of milk protein allergy and 1 case of egg white allergy.The patients had acute vomiting [5 cases (100%)], diarrhea [4 cases (80%)], early shock symptoms [5 cases (100%)], transient fever [2 cases (40%)]. Hematogenous leukocytes were increased in 3 cases (60%), C-reactive protein was increased in 1 case (20%), faecal leukocytes(+ )[2 cases (40%)], occult blood (+ ) [1 case (20%)]. Four cases were tested for food allergen specific IgE, of which 2 cases (40%) were positive for milk protein.After avoiding allergens, 3 patients (60%) needed intravenous rehydration treatment and 2 cases (40%) received oral rehydration treatment.The above 5 cases recovered quickly.Three patients (60%) used antibiotics.Four cases (80%) of the first-degree relatives of FPIES had a clear history of allergy.Families of children with FPIES had low awareness of the disease before the diagnosis was made, and the allergens were strictly avoided according to the doctor′s instructions after the diagnosis was made.Similar allergic reactions did not occur again, and complementary foods were gradua-lly added under the guidance of the doctor.Two patients had multiple food allergies.The body weight and length of 2 children with growth retardation were catching up with each other.Conclusions:FPIES is a serious food allergy related gastrointestinal disease which is easy to be misdiagnosed clinically.The diagnosis requires a combination of the family and personal allergy history, diet records, the characteristic performance of disease onset, the effect of diet avoi-dance and the necessary differential diagnosis.The long-term management and monitoring after diagnosis is also very important.

Síndrome de enterocolitis inducida por proteínas alimentarias por ingesta de kiwi como causa de evento potencialmente grave inexplicado en una niña / Food Protein Induced Enterocolitis Syndrome due to ingestion of kiwi causing potentially severe unexplained event in a child

El síndrome de enterocolitis inducida por proteínas alimentarias es una alergia alimentaria no mediada por inmunoglobulina E que se manifiesta clínicamente con vómitos profusos y repetitivos, en ocasiones, asociados a diarrea, y puede llegar a asociar deshidratación y letargia, con riesgo de desarrollo de shock. A pesar de su potencial gravedad, el índice de sospecha de este síndrome es bajo, lo que demora su diagnóstico, especialmente, en aquellos casos que son desencadenados por alimentos sólidos. La presencia de vómitos y la duración de más de un minuto son los datos clave que pueden diferenciarlo de los episodios breves, resueltos e inexplicados. Se presenta el caso de una lactante de 6 meses de vida con diagnóstico final de síndrome de enterocolitis inducida por proteínas alimentarias por ingesta de kiwi.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE food allergy manifesting as profuse, repetitive vomiting, sometimes with diarrhea, leading to dehydration and lethargy that can be severe and lead to shock. Despite the potential severity, awareness of FPIES is low and diagnosis is often delayed, especially in those triggered by solid foods. Presence of vomits and duration of more than 1 minute are the key differential factors to distinguish FPIES from brief resolved unexplained events. We report a case of a 6-month-old infant finally diagnosed as having kiwi induced FPIES.

Severe forms of food allergy / Formas graves de alergia alimentar

Abstract Objectives: To guide the diagnostic and therapeutic management of severe forms of food allergy. Data sources: Search in the Medline database using the terms "severe food allergy," "anaphylaxis and food allergy," "generalized urticaria and food allergy," and "food protein-induced enterocolitis syndrome" in the last ten years, searching in the title, abstract, or keyword fields. Summary of data: Food allergy can be serious and life-threatening. Milk, eggs, peanuts, nuts, walnuts, wheat, sesame seeds, shrimp, fish, and fruit can precipitate allergic emergencies. The severity of reactions will depend on associated cofactors such as age, drug use at the onset of the reaction, history and persistence of asthma and/or severe allergic rhinitis, history of previous anaphylaxis, exercise, and associated diseases. For generalized urticaria and anaphylaxis, intramuscular epinephrine is the first and fundamental treatment line. For the treatment in acute phase of food-induced enterocolitis syndrome in the emergency setting, prompt hydroelectrolytic replacement, administration of methylprednisolone and ondansetron IV are necessary. It is important to recommend to the patient with food allergy to maintain the exclusion diet, seek specialized follow-up and, in those who have anaphylaxis, to emphasize the need to carry epinephrine. Conclusion: Severe food allergy may occur in the form of anaphylaxis and food-protein-induced enterocolitis syndrome, which are increasingly observed in the pediatric emergency room; hence, pediatricians must be alert so they can provide the immediate diagnosis and treatment.

Resumo Objetivos: Abordar o manejo diagnóstico e terapêutico das formas graves de alergia alimentar. Fontes dos dados: Busca ativa na base de dados Medline dos termos severe food allergies, anaphylaxis and food allergy e food protein-induced enterocolitis nos últimos dez anos e com busca nos campos título, resumo ou palavra-chave. Síntese dos dados: A alergia alimentar pode ser grave e ameaçadora à vida. Leite, ovo, amendoim, castanha, noz, trigo, gergelim, crustáceo, peixe e frutas podem precipitar emergências alérgicas. A gravidade das reações vai depender de fatores associados, tais como idade, uso de medicamentos no início da reação, persistência de asma e/ou rinite alérgica grave, história de prévia anafilaxia, exercício e doenças intercorrentes. Para anafilaxia, a adrenalina intramuscular é uma indicação bem estabelecida. Para o tratamento da síndrome da enterocolite induzida pela proteína alimentar na fase aguda no setor de emergência, fazem-se necessárias a pronta reposição hidroeletrolítica e a administração de metilprednisolona e odansetrona IV. Importante recomendar ao paciente com o diagnóstico de alergia alimentar grave que mantenha a dieta de exclusão, procure acompanhamento especializado e, naqueles que apresentaram anafilaxia, enfatizar a necessidade de portar adrenalina. Conclusão: Alergia alimentar grave pode se manifestar como anafilaxia ou síndrome da enterocolite induzida por proteína alimentar em fase aguda, as quais, por serem condições cada vez mais presentes e reconhecidas no setor de emergência pediátrica, demandam diagnóstico e tratamento imediatos.

Food protein-induced enterocolitis syndrome / 国际儿科学杂志

Food protein-induced enterocolitis syndrome(FPIES) is a series symptoms of recurrent vomiring and diarrhea caused by non-IgE-mediated food allergy to cow milk and soy in infants.The most common causative foods of FPIES are cow milk,soy and rice.Symptoms start within first days to 12 months of life.The sensitivity is usually outgrown by 3 years of age.The most common clinical symptoms observed include recurrent vomiting,diarrhea,fecal bloody,lethargy,pallor,etc.The diagnosis relies on history,clinical features,food eliminate,and oral food challenges.The food elimination is the mains treatment of FPIES management.

Food protein-induced enterocolitis syndrome caused by cow's milk protein allergy in an infant：case report and review of literature / 临床儿科杂志

To discuss clinical diagnosis and treatment of cow’s milk protein allergy and cow’s milk protein-induced FPIES (food protein induced enterocolitis syndrome). Methods We retrospectively analyzed clinical data of one infant with milk protein allergy-induced FPIES. Results A 67 days old female on mixed breast and formula feeding developed recurrent diarrhea, abdominal distension, vomiting, mucousy and bloody stools, feeding dififculty, anemia, and failure to thrive since 2 weeks after birth. Laboratory studies showed anemia, increased CRP level and elevation of peripheral white blood count and eosinophil proportion. Milk-speciifc IgE was negative. She was previously hospitalized 4 times, all with admitting diagnosis of“necrotizing enterocolitis”. We treated her with milk protein elimination for 4 weeks and all symptoms were resolved. Milk protein re-challenge test was positive, consistent with clinical features of cow’s milk protein allergy-induced infant FPIES. Conclusions Cow’s milk protein allergy and cow’s milk protein-induced FPIES can present with non-speciifc and variable clinical symptoms and signs, and should be considered in the differential diagnosis.

Is This Symptom Even a Food Allergy?: Clinical Types of Food Protein-induced Enterocolitis Syndrome / 대한소아소화기영양학회지

Food protein-induced enterocolitis syndrome (FPIES) is an under-recognized non-IgE-mediated gastrointestinal food allergy. The diagnosis of FPIES is based on clinical history, sequential symptoms and the timing, after excluding other possible causes. It is definitively diagnosed by an oral food challenge test. Unfortunately, the diagnosis of FPIES is frequently delayed because of non-specific symptoms and insufficient definitive diagnostic biomarkers. FPIES is not well recognized by clinicians; the affected infants are often mismanaged as having viral gastroenteritis, food poisoning, sepsis, or a surgical disease. Familiarity with the clinical features of FPIES and awareness of the indexes of suspicion for FPIES are important to diagnose FPIES. Understanding the recently defined clinical terms and types of FPIES is mandatory to suspect and correctly diagnose FPIES. The aim of this review is to provide a case-driven presentation as a guide of how to recognize the clinical features of FPIES to improve diagnosis and management of patients with FPIES.

Síndrome de enterocolitis inducido por proteínas de la dieta: reporte de casos / Food protein Induced enterocolitis: two case reports

A propósito de 2 casos clínicos de pacientes con antecedente de enterocolitis neonatal, se presenta el temade síndrome de enterocolitis inducido por proteínas de la dieta. Este es un tipo de alergia alimentaria no mediada por Ig E, de presentación severa, con incidencia y prevalencia desconocidas y cuya sospecha clínica, diagnóstico y manejo oportuno, se anteponen al desarrollo de complicaciones severas que incluso pueden llevar a la muerte.

Two case reports of patients with neonatal enterocolitis present the topic of Food Protein-Induced EnterocolitisSyndrome (FPIES). FPIES is a type of food allergy which is not mediated by IgE and which has a severe presentation.Its incidence and prevalence are unknown. Clinical suspicion, diagnosis, and timely management are important in light of likely development of severe complications which can even lead to death.

Apoptosis and upregulation of TNF-alpha and TRAIL receptor 1 (DR4) in the pathogenesis of food protein-induced enterocolitis syndrome / 소아과

PURPOSE: Expression levels of tumor necrosis factor (TNF)-alpha expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF-alpha has been reported to induce apoptotic cell death in the epithelial cells. We studied the TNF family and TNF-receptor family apoptosis on the duodenal mucosa to investigate their roles in the pathogenesis of FPIES. METHODS: Fifteen infants diagnosed as having FPIES using standard oral challenge test and 5 controls were included. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to identify the apoptotic cell death bodies. Immunohistochemical staining of TNF-alpha, Fas ligand (FasL) for TNF family and TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), and Fas for TNF-receptor family were performed to determine the apoptotic mechanisms. RESULTS: TUNEL+ was significantly more highly expressed in the duodenal mucosa of FPIES patients than in controls (P=0.043). TNF-alpha (P=0.0001) and DR4 (P=0.003) were significantly more highly expressed in FPIES patients than in controls. Expression levels of FasL, Fas, and DR5 were low in both groups and were not significantly different between the 2 groups. CONCLUSION: These results suggest that FPIES pathogenesis is induced by apoptosis, and that TNF-alpha expression and DR4 pathway may have an important role in apoptosis.

Food Protein-induced Enterocolitis Syndrome:an Update on Clinical Approaches and Its Pathophysiology / 대한소아소화기영양학회지

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated hypersensitivity disorder, which is associated with mainly gastrointestinal symptoms and has a delayed onset. The vomiting and/or diarrheal symptoms of FPIES typically begin in the first month of life in association with a failure to thrive, metabolic acidosis, and shock. Therefore, the differential diagnosis of FPIES and neonatal or infantile sepsis-like illnesses or gastroenteritis is difficult. The early recognition of indexes of suspicion for FPIES may help in the diagnosis and treatment of this disorder. The diagnosis of FPIES is generally made through clinical practice and food-specific IgE test findings are typically negative in this condition. Therefore, oral cow's milk challenge (OCC) remains the valid diagnostic standard for FPIES. An investigation of positive OCC outcomes helps to find out a diagnostic algorithm of criteria of a positive challenge in FPIES. Moreover, it has not been clearly determined in infantile FPIES when 1st follow up-oral food challenge (FU-OFC) should be performed, with what kind of food protein (e.g., cow's milk, soy), and how much protein should be administered. Hence, to prevent the risk of inappropriate FU-OFC or accidental exposure and achieve appropriate dietary management, it is necessary to identify tolerance rates to major foods under the careful follow up of infantile FPIES patients. On the other hand, small intestinal enteropathy with villous atrophy is observed in FPIES and this enteropathy seems to be in part induced by both of epithelial apoptosis and intercellular junctional complex breakdown. The purpose of this report is to introduce an update on diagnostic and therapeutic approaches in FPIES and suggest the possible histopathological evidences in this disorder.

Food Protein-induced Enterocolitis Syndrome:an Update on Clinical Approaches and Its Pathophysiology / 대한소아소화기영양학회지

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated hypersensitivity disorder, which is associated with mainly gastrointestinal symptoms and has a delayed onset. The vomiting and/or diarrheal symptoms of FPIES typically begin in the first month of life in association with a failure to thrive, metabolic acidosis, and shock. Therefore, the differential diagnosis of FPIES and neonatal or infantile sepsis-like illnesses or gastroenteritis is difficult. The early recognition of indexes of suspicion for FPIES may help in the diagnosis and treatment of this disorder. The diagnosis of FPIES is generally made through clinical practice and food-specific IgE test findings are typically negative in this condition. Therefore, oral cow's milk challenge (OCC) remains the valid diagnostic standard for FPIES. An investigation of positive OCC outcomes helps to find out a diagnostic algorithm of criteria of a positive challenge in FPIES. Moreover, it has not been clearly determined in infantile FPIES when 1st follow up-oral food challenge (FU-OFC) should be performed, with what kind of food protein (e.g., cow's milk, soy), and how much protein should be administered. Hence, to prevent the risk of inappropriate FU-OFC or accidental exposure and achieve appropriate dietary management, it is necessary to identify tolerance rates to major foods under the careful follow up of infantile FPIES patients. On the other hand, small intestinal enteropathy with villous atrophy is observed in FPIES and this enteropathy seems to be in part induced by both of epithelial apoptosis and intercellular junctional complex breakdown. The purpose of this report is to introduce an update on diagnostic and therapeutic approaches in FPIES and suggest the possible histopathological evidences in this disorder.

Expression of Transforming Growth Factor-beta Receptors in Food Protein-Induced Enterocolitis Syndrome in Infancy / 소아알레르기및호흡기학회지

PURPOSE: Food protein-induced enterocolitis syndrome (FPIES) is a symptom complex of vomiting and diarrhea caused by non-IgE mediated allergy to cow's milk and/or soy in young infants. Transforming growth factor (TGF)-beta has been reported to protect the epithelial barrier of the gut from foreign antigens. We studied the expression of type 1 and 2 TGF-beta receptors in the mucosa of small intestine to investigate their roles in the pathogenesis of FPIES. METHODS: Twenty-eight patients, aged 7 to 120 days (mean 49 days) who were diagnosed with FPIES by clinical criteria and challenge tests were included. Immunohistochemical stainings for type 1 and 2 TGF-beta receptors were performed on endoscopic duodenal biopsy specimens. RESULTS: Type 1 and 2 TGF-beta receptors were expressed in the villous and crypt epithelial cells but nearly absent in the lamina propria in both patients and controls. Type 1 TGF-beta receptor expression was significantly lower in the patients who had villous atrophy than in the patients who had not and in controls. The expression of type 1 TGF-beta receptor was negatively correlated with the severity of villous atrophy. Type 2 TGF-beta receptor expression showed no significant difference between the patients and controls. CONCLUSION: Our results suggests that the decreased activity of type 1 TGF-beta receptor is implicated in the pathogenesis of FPIES in young infants.

A Case of Milk Protein Induced Enterocolitis Syndrome / 대한소아소화기영양학회지

Food allergy is a disease caused by an abnormal immunological reaction to specific food proteins. Whole milk and soy beans are the most frequent causes of food allergy, some studies show that 2.2~2.8% of children aged between 1 and 2 year are allergic to milk. It can be classified to acute (urticaria, asthma, anaphylaxis) or chronic (diarrhea, atopic dermatitis) allergy according to clinical symptoms, or to IgE related or non IgE related allergy by an immunological aspect. Generally, allergies invading only the GI tract are mostly due to a non IgE related reaction. These hypersensitive, immunologic reactions of the GI tract, not related to specific IgE for food, present themselves in many ways such as food protein-induced enteropathy, food protein-induced enterocolitis syndrome (FPIES), celiac disease, food induced protocolitis, or allergic eosinophillic gastroenteritis. FPIES is one kind of non IgE related allergic reaction and is manifested as severe vomiting and diarrhea in infants between 1 week and 3 months. We report a case of FPIES in a 40-day old male infant presenting with 3 times of repeated events of watery diarrhea after cow's milk feeding.