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.

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.

Severe Food Protein-Induced Enterocolitis Syndrome After Hematopoietic Stem Cell Transplantation: Pediatric Case Report.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. In the last few years, after the publication of the consensus guidelines, with refined diagnostic criteria and improved awareness, FPIES is diagnosed with increased frequency. However, despite having a background of immune dysregulation, this complication has just been described once in the posttransplant setting, in an adult patient. To the best of our knowledge, there are no reports of pediatric patients developing FPIES after a hematopoietic stem cell transplant (HCT). METHODS: Retrospective review of a pediatric patient who developed severe FPIEs after a HCT. RESULTS: In this case report, the clinical presentation and diagnosis challenges of a pediatric patient who developed severe FPIES after HCT are described. The patient developed severe vomiting, diarrhea, lethargy, and shock and required admission to the pediatric intensive care unit in three occasions before the diagnosis was made. CONCLUSIONS: To the best of our knowledge, this is the first report of severe FPIES post-HCT in a pediatric patient. Physicians who are looking after pediatric patients in the post-HCT setting need to be aware of this possibility and include this entity in the differential diagnosis in order to reduce its associated morbidity.

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 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.

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.

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.

Early infancy dysbiosis in food protein-induced enterocolitis syndrome: A prospective cohort study.

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.

A Systematic Review of Food Protein-Induced Enterocolitis Syndrome.

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.

Comparison of adult food protein-induced enterocolitis syndrome to crustaceans and immediate-type food allergy.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is increasingly found in adults. FPIES requires different treatment from immediate-type food allergy (FA) in emergency medicine. However, no comparison of the clinical presentations of these diseases has been reported. OBJECTIVE: To compare the clinical presentations and causative crustaceans of adult FPIES and FA using a standardized questionnaire and to thereby lay the groundwork for establishing an algorithm that distinguishes those diseases. METHODS: We conducted a retrospective cohort study of crustacean-avoidant adults by telephone interview based on the previously reported diagnostic criteria for adult FPIES to compare the clinical features and crustacean intake status between FPIES and FA. RESULTS: Of 73 adult patients with crustacean allergy, 8 (11%) were diagnosed with having FPIES and 53 (73%) FA. Compared with the patients with FA, those with FPIES had a longer latency period (P < .01), more episodes (P = .02), longer duration of symptoms (P = .04), more frequent abdominal distention (P = .02), and severe colic pain (P = .02). Half of the patients with FPIES experienced fear of death during an episode. Panulirus japonicus (Japanese spiny lobster) and Homarus weber (lobster) were significantly common FPIES-causing foods. A statistically significant 62.5% of patients with FPIES were able to ingest some type of crustacean. CONCLUSION: FPIES and FA can be clearly differentiated by the abdominal symptoms, latency period, and duration of episodes. Furthermore, some patients with FPIES do not necessarily need to avoid all crustaceans. Our findings lay the groundwork for establishing an algorithm that distinguishes FPIES from FA in adults.

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.

Food protein-induced enterocolitis syndrome due to buckwheat: A case report.

Buckwheat is a rare causative food for food protein-induced enterocolitis syndrome (FPIES). To date, it is unknown what laboratory data patients with FPIES caused by buckwheat show. We report a 4-year-old female with FPIES caused by buckwheat and the laboratory results. Skin prick, specific IgE antibody, and basophil activation tests were negative; however, the lymphocyte stimulation test (LST) revealed a 10.2-fold increase in activation compared with the negative control. In an open-label oral food challenge (OFC) of 80 g boiled buckwheat noodles, 3 hours after ingestion, vomiting occurred four times in a 2-hour duration. Therefore, we diagnosed the patient with FPIES caused by buckwheat. Her neutrophil count, C-reactive protein, and thymus and activation-regulated chemokine were elevated after the OFC. Moreover, the patient had a positive reaction to the LST, which may theoretically be useful in diagnosing non-immunoglobulin E-mediated gastrointestinal food allergies. FPIES caused by buckwheat is rare; however, we found that the same laboratory results were observed in a comparison of FPIES cases caused by other foods.

Drug-Induced Enterocolitis Syndrome in Children.

Drug-Induced Enterocolitis Syndrome (DIES) is a drug-induced hypersensitivity reaction non-IgE mediated involving the gastrointestinal system that occurs 2 to 4 h after drug administration. Antibiotics, specifically amoxicillin or amoxicillin/clavulanate, represent the most frequent drugs involved. Symptoms include nausea, vomiting, abdominal pain, diarrhea, pallor, lethargy, and dehydration, which can be severe and result in hypovolemic shock. The main laboratory finding is neutrophilic leukocytosis. To the best of our knowledge, 12 cases of DIES (9 children-onset and 3 adult-onset cases) were described in the literature. DIES is a rare clinically well-described allergic disease; however, the pathogenetic mechanism is still unclear. It requires to be recognized early and correctly treated by physicians.

Differences in Thymus and Activation-Regulated Chemokine and Squamous Cell Carcinoma Antigen 2 Levels in Food Protein-Induced Enterocolitis Syndrome and Atopic Dermatitis.

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.

Evaluation of the Clinical Characteristics of Patients with Food Protein-Induced Enterocolitis Syndrome: A Multicenter Study.

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.

Potential of Thymus and Activation-Regulated Chemokine (TARC) as a Prognostic Biomarker of Food Protein-Induced Enterocolitis Syndrome (FPIES) Caused by Egg Yolk.

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.

The history of the drug-induced enterocolitis syndrome.

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.

Differentiation of food protein-induced enterocolitis syndrome misleading to necrotizing enterocolitis.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a rare non-immunoglobulin E-mediated food allergy with necrotizing enterocolitis (NEC)-like symptoms which requires differential diagnosis as treatments differ. OBJECTIVE: To evaluate the clinical, laboratory, and radiologic findings that differentiate FPIES from NEC in preterm and term infants. METHODS: Clinical features, comorbidities, and laboratory and radiologic findings of neonates with presumed NEC were reviewed retrospectively and compared between FPIES and NEC in preterm and term infants who were admitted to the neonatal intensive care unit at Seoul National University Bundang Hospital between May 2003 and February 2020. RESULTS: A total of 10 of 150 (6.7%) preterm and 17 of 38 (44.7%) term infants with presumed NEC were confirmed to have FPIES; the remainder had NEC by modified Bell's criteria. Demographics and comorbidities were similar between these groups. Symptoms such as hematochezia, shock, leukocytosis, peripheral eosinophilia, and feeding of extensively hydrolyzed milk formula or elemental formula after discharge were significantly different between the 2 groups in term infants (P <.05), but not in preterm infants. On abdominal ultrasonography, pneumatosis intestinalis was more common among preterm FPIES (44.4%) than NEC cases (21.6%) (P =.04). Among the preterm infants, 4 FPIES (40%) and 25 NEC (17.9%) cases required surgery (P =.10). CONCLUSION: Differentiating FPIES in neonates suspected of having NEC is important as dietary elimination of the triggering milk protein can be recommended instead of prolonged fasting and antibiotic treatment, which are indicated for NEC, in both term and preterm infants.

Update on Food Protein-Induced Enterocolitis Syndrome (FPIES).

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. 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.