Heterogeneity of food protein-induced enterocolitis syndrome (FPIES).

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with gastrointestinal symptoms such as vomiting and diarrhea. The development of international consensus guidelines for the diagnosis and management of FPIES in 2017 enabled us to compare patients worldwide, regardless of geographic variation in disease features. As a result, it has become clear that there is heterogeneity among patients with FPIES or that there are cases that partly fit the diagnostic criteria for FPIES but have different characteristics. This review highlights the heterogeneity in FPIES characteristics in terms of trigger foods, the age of onset, differences in geographic regions, and symptoms; it further proposes four disease entities, including acute FPIES in children, acute FPIES in adults, chronic FPIES, and early-onset neonatal FPIES, depending on the age of onset and presumed pathophysiology. The major symptoms at onset and trigger foods differ in acute FPIES in children, acute FPIES in adults, and chronic FPIES, whereas the disease entities may share a similar pathophysiology. Early-onset neonatal FPIES may have a different pathophysiology than acute or chronic FPIES, and may not necessarily fulfil the full diagnostic criteria for acute or chronic FPIES described in the international consensus guidelines. Due to the similarity in symptoms, early-onset neonatal FPIES may sometimes be misdiagnosed as necrotizing enterocolitis. We aim to increase awareness of FPIES among medical staff in pediatrics, neonatology, and internal medicine and promote research, to gain a better understanding of the heterogeneity and pathophysiology of FPIES.

Current and future perspectives on the consensus guideline for food protein-induced enterocolitis syndrome (FPIES).

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy presenting with delayed onset of projectile vomiting in the absence of cutaneous and respiratory symptoms. The pathophysiology of FPIES remains poorly characterized. The first international consensus guidelines for FPIES were published in 2017 and provided clinicians with parameters on the diagnosis and treatment of FPIES. The guidelines have served as a resource in the recognition and management of FPIES, contributing to an increased awareness of FPIES. Since then, new evidence has emerged, shedding light on adult-onset FPIES, the different phenotypes of FPIES, the recognition of new food triggers, center-specific food challenge protocols and management of acute FPIES. Emerging evidence indicates that FPIES impacts both pediatric and adult population. As a result, there is growing need to tailor the consensus guidelines to capture diagnoses in both patient groups. Furthermore, it is crucial to provide food challenge protocols that meet the needs of both pediatric and adult FPIES patients, as well as the subset of patients with atypical FPIES. This review highlights the evolving clinical evidence relating to FPIES diagnosis and management published since the 2017 International FPIES Guidelines. We will focus on areas where recent published evidence may support evolution or revision of the guidelines.

Discrepancy between Caregivers' Reports and Physicians' Evaluation of Causative Foods in Food Protein-Induced Enterocolitis Syndrome in Japan: The Japan Environment and Children's Study.

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.

Eosinophilic enterocolitis: a case report.

BACKGROUND: Eosinophilic enterocolitis is a rare disorder characterized by abnormal eosinophilic infiltration of the small intestine and the colon. CASE PRESENTATION: We report a case of a 29-year-old White man, who presented with an acute bowel obstruction. He had a history of a 2 months non-bloody diarrhea. An abdominal computed tomography (CT) and a MR enterography showed a multifocal extensive ileitis. White blood cell and eosinophilic polynuclei count was elevated (700/mm3). Ileo-colonoscopy showed normal ileum and segmental petechial colitis. Pathology showed a high eosinophilic infiltration in the colon. The patient was treated with steroids, with a clinical, biological and radiological recovery. CONCLUSION: Eosinophilic enterocolitis should be kept in mind as a rare differential diagnosis in patients presenting with small bowel obstruction.

Clinical relevance of inflammation on rectal biopsy for Hirschsprung disease: An outcomes analysis.

OBJECTIVES: Inflammation on diagnostic rectal biopsy for children with suspected Hirschsprung disease (HSCR) is reported on pathology, and its significance is unknown. We describe the management and outcomes of a cohort with inflammation on rectal biopsy compared to those without. Specifically, to address the hypothesis that inflammation on diagnostic biopsy is associated with increased complication rates irrespective of intervention type and timing. METHODS: A single institution retrospective review of children with HSCR who underwent biopsy and endorectal pull-through (ERPT) from 2010 to 2020 was performed. The primary outcome was overall complications at 30-days following ERPT. Secondary outcomes included timing and type of operative intervention as well as postoperative enterocolitis diagnosed within 6-months of ERPT. RESULTS: Forty-nine children were identified; inflammation was present on diagnostic biopsy for 17 children. Those with inflammation were more likely to have clinical evidence of enterocolitis at the time of biopsy (p = 0.001) and were more likely to undergo leveling colostomy before ERPT (p = 0.01). Children with inflammation had a higher anastomotic leak rate (p = 0.04). Subgroup analysis of patients with inflammation undergoing primary ERPT versus leveling colostomy demonstrated no significant difference in outcomes following definitive ERPT. CONCLUSIONS: Our study suggests inflammation on diagnostic rectal biopsy for HSCR is associated with increased anastomotic leak rates. While additional prospective studies are indicated, attention to methods of mitigating inflammation and confirming its resolution before definitive pull-through may be of benefit for improving clinical outcomes in patients found with inflammation on diagnostic rectal biopsy.

A nationwide survey of non-IgE-mediated gastrointestinal food allergies in neonates and infants.

BACKGROUND: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups. METHODS: We conducted a nationwide cross-sectional survey of non-IgE-GIFAs in Japan from April 2015 through March 2016. A questionnaire was sent to hospitals and clinics throughout Japan. The questionnaire asked about the number of physician-diagnosed non-IgE-GIFA patients, the status of fulfillment of the diagnostic criteria, tentative classification into 4 clusters based on the initial symptoms, the day of onset after birth, complications, and the suspected offending food(s). RESULTS: The response rate to that questionnaire was 67.6% from hospitals and 47.4% from clinics. Analyses were conducted about "diagnosis-probable" patient cohort (n = 402) and the "diagnosis-confirmed" patients (n = 80). In half of the reported non-IgE-GIFA patients, onset occurred in the neonatal period. The patients were evenly distributed among 4 non-IgE-GIFA clusters. In Cluster 1, with symptoms of vomiting and bloody stool, the onset showed a median of 7 days after birth, which was the earliest among the clusters. Cow's milk was the most common causative food. CONCLUSIONS: In half of the patients, the onset of non-IgE-GIFAs was in the neonatal period. This highlights the importance of studying the pathogenesis in the fetal and neonatal periods.

Late Diagnosis of Hirschsprung Disease: Clinical Presentation and Long-Term Functional Outcomes.

PURPOSE: Hirschsprung Disease (HD) is typically diagnosed in the neonatal period. A small subset of patients have a prolonged course of abdominal distention and constipation prior to diagnosis. Late HD is defined as having been diagnosed at greater than or equal to one year of age. The literature is limited and offers conflicting data on the implications of a late diagnosis. We aim to investigate the presentation, operative approach, and functional outcomes of a large cohort of patients with a late HD diagnosis. METHODS: All patients with a late diagnosis of HD (after 1 year of age) at our institution between 1997 and 2021 were included. RESULTS: Twenty-eight patients were diagnosed with HD at a median age of 3.4 years. Chronic constipation, failure to thrive, and enterocolitis occurred in 100 %, 31 %, and 14 %, respectively. All patients underwent contrast enema and biopsies during their workup, identifying primarily rectosigmoid disease (n = 27) and total colonic aganglionosis (n = 1). Surgical intervention was performed in 27 patients, with 4 patients (15 %) needing a stoma (3 with plan for staged pull-through, 1 long-term stoma) and 23 patients (85 %) undergoing a single-stage pull-through. Postoperative complications included Hirschsprung-associated enterocolitis (n = 5), ostomy prolapse and revision (n = 2), abdominal distention requiring ileostomy creation (n = 2), redo pull-through (n = 2), retroperitoneal hematoma (n = 1), and cecostomy tube placement (n = 1). At a median follow-up of 5.4 years, 83 % of eligible patients achieved fecal continence with 43 % needing laxatives for persistent constipation. CONCLUSION: Recognizing a late presentation of HD requires a high index of suspicion. Patients with a late diagnosis did not experience an increased rate of permanent stoma, complications, or redo surgery compared to rates reported for the larger HD population. Similar long-term functional outcomes were achieved compared to the larger HD population. LEVEL OF EVIDENCE: IV.

A detailed intake-status profiling of seafoods in adult food-protein-induced enterocolitis syndrome patients.

BACKGROUND: Adults with food-protein-induced enterocolitis syndrome (FPIES) often develop severe abdominal symptoms after eating seafood. However, no investigation of a food elimination strategy for adult FPIES patients has been performed to date. METHODS: We conducted a retrospective cohort study of seafood-avoidant adults by telephone interview, based on the diagnostic criteria for adult FPIES reported by González et al. We compared the clinical profiles, abdominal symptoms, and causative seafoods between FPIES and immediate-type food allergy (IgE-mediated FA) patients. We also profiled the detailed intake-status of seafoods in adult FPIES patients. RESULTS: Twenty-two (18.8 %) of 117 adults with seafood-allergy were diagnosed with FPIES. Compared with the IgE-mediated FA patients, FPIES patients had an older age of onset, more pre-existing gastrointestinal and atopic diseases, more episodes, longer latency and duration of symptoms, more nausea, abdominal distention, and severe abdominal pain, and more frequent vomiting and diarrhea. In particular, abdominal distention-reflecting intestinal edema and luminal fluid retention-may be the most distinctive characteristic symptom in adult FPIES (p < 0.001). Bivalves, especially oysters, were the most common cause of FPIES. Strikingly, intake-status profiling revealed that many FPIES patients can safely ingest an average of 92.6 % of seafood species other than the causative species. CONCLUSIONS: There are many differentiators between FPIES and IgE-mediated FA, which may reflect differences in the underlying immunological mechanisms. Although seafood FPIES is unlikely to induce tolerance, many patients can ingest a wide variety of seafood species after a long period from onset.

Gastroenterocolite eosinofílica - uma causa rara de diarreia / Eosinophilic gastroenterocolitis - a rare cause of diarrhea

Introdução: Colite eosinofílica é uma doença crônica rara. Pode ser idiopática ou estar associada à alergias alimentares e à doenças atópicas. Assim, a incidência é, muitas vezes, indefinida devido ao seu subdiagnóstico. Objetivo: Relatar o caso de uma paciente com colite eosinofílica e dermatite atópica. Método: Trata-se de um estudo tipo Relato de Caso utilizando dados do prontuário clínico, de uma paciente jovem que evoluiu com quadro de dor abdominal e diarreia sanguinolenta e que, após investigação por meio de exames laboratoriais, diversos exames de imagem, o resultado anatomopatológico evidenciou Ileíte eosinofílica. Resultados: O tratamento consistiu em mudança alimentar e uso de budesonida por via oral, havendo regressão do quadro e melhora da dermatite atópica. Conclusão: É necessário excluir a Colite Eosinofílica secundária, pois pode ser uma manifestação à diversas patologias, já que tem apresentação clínica inespecífica

Introducion: Eosinophilic colitis is a rare chronic disease. It may be idiopathic or associated with food allergies and atopic diseases. Thus, the incidence is often undefined due to underdiagnosis. Objective: To report the case of a patient with eosinophilic colitis and atopic dermatitis. Method: This is a case report study using data from the clinical record, of a young patient who developed abdominal pain and bloody diarrhea and who, after investigation through laboratory tests, several imaging tests, the result pathology showed eosinophilic ileitis. Results: Treatment consisted of dietary changes and oral budesonide, resulting in regression of the condition and improvement in atopic dermatitis. Conclusion: It is necessary to exclude secondary Eosinophilic Colitis, as it can be a manifestation of several pathologies, as it has a nonspecific clinical presentation

Introducción: La colitis eosinofílica es una enfermedad crónica rara. Puede ser idiopática o estar asociada a alergias alimentarias y enfermedades atópicas. Por tanto, la incidencia suele estar indefinida debido a un infradiagnóstico. Objetivo: Reportar el caso de un paciente con colitis eosinofílica y dermatitis atópica. Método: Se trata de un estudio de reporte de caso, utilizando datos de la historia clínica, de un paciente joven que desarrolló dolor abdominal y diarrea sanguinolenta y quien, luego de la investigación mediante pruebas de laboratorio, varias pruebas de imagen, el resultado de la patología arrojó ileítis eosinofílica. Resultados: El tratamiento consistió en cambios dietéticos y budesonida oral, lo que resultó en regresión del cuadro y mejoría de la dermatitis atópica. Conclusión: Es necesario excluir la Colitis Eosinofílica secundaria, ya que puede ser manifestación de varias patologías, al tener una presentación clínica inespecífica

Severe Immune-Related Enteritis after In Utero Exposure to Pembrolizumab.

Immune checkpoint blockade has become standard treatment for many types of cancer. Such therapy is indicated most often in patients with advanced or metastatic disease but has been increasingly used as adjuvant therapy in those with early-stage disease. Adverse events include immune-related organ inflammation resembling autoimmune diseases. We describe a case of severe immune-related gastroenterocolitis in a 4-month-old infant who presented with intractable diarrhea and failure to thrive after in utero exposure to pembrolizumab. Known causes of the symptoms were ruled out, and the diagnosis of pembrolizumab-induced immune-related gastroenterocolitis was supported by the results of histopathological assays, immunophenotyping, and analysis of the level of antibodies against programmed cell death protein 1 (PD-1). The infant's condition was successfully treated with prednisolone and infliximab.

Pearls and pitfalls in food protein-induced enterocolitis syndrome (FPIES).

Background: Food protein-induced enterocolitis syndrome (FPIES) is a rare, non-immunoglobulin E (IgE) mediated gastrointestinal food hypersensitivity. It is a clinical diagnosis commonly characterized by profuse vomiting 1 to 4 hours after ingestion of the triggering food(s). Objective: The objective was to increase awareness of FPIES and review the epidemiology, clinical presentation, pathogenesis, diagnosis, and management of FPIES. The lack of availability of a definite biomarker or diagnostic tool often leads to a delay in diagnosis. Methods: A literature search of salient articles that described case reports and case series of FPIES and their management were analyzed. Results: A case of FPIES with a literature review is presented with emphasis on clinical pearls and pitfalls. FPIES is a diagnosis of exclusion and the mainstay of treatment is avoidance of the trigger food(s) for at least 12-18 months from the last exposure. Conclusion: As FPIES is a non-IgE-mediated reaction, allergy testing via skin-prick test or blood tests to measure food IgE antibodies is not routinely recommended. Many children outgrow FPIES by 3-4 years of age. Supervised oral food challenge is recommended to assess acquisition of tolerance.