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.

Clinical characteristics and influence of postoperative Hirschsprung-associated enterocolitis: retrospective study at a tertiary children's hospital.

PURPOSE: To explore the influence of postoperative Hirschsprung-associated enterocolitis (post-HAEC) on long-term outcomes and to identify risk factors of post-HAEC. METHODS: The medical records of 304 eligible patients diagnosed with Hirschsprung's disease (HSCR) were reviewed. We analyzed the clinical characteristics of post-HAEC and its influence on long-term outcomes. Furthermore, risk factors for early and recurrent HAEC were identified separately. RESULTS: The overall incidence of post-HAEC was 29.9% (91/304). We categorized early HAEC as occurring within postoperative 3 months (n = 39) and recurrent HAEC as occurring ≥ 3 episodes within postoperative 6 months (n = 25). Patients with early HAEC were more likely to experience worse nutritional status, defecation function, and quality of life compared to those with late or no episodes (P < 0.05). Similarly, the adverse influences of recurrent HAEC on these outcomes were also significant (P < 0.05). The risk factors for early HAEC included preoperative undernutrition, long-segment HSCR, and postoperative Grade 3-4 complications within 30 days. For recurrent HAEC, risk factors were preoperative malnutrition, non-parental caregivers, long-segment HSCR, and postoperative Grade 3-4 complications within 30 days. CONCLUSION: Classification of post-HAEC based on the first episode time and frequency was necessary. The earlier or more frequent episodes of post-HAEC have detrimental influences on long-term outcomes. Furthermore, risk factors for early and recurrent HAEC were different.

Recent trends in food protein-induced enterocolitis syndrome (FPIES).

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.

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.

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.

Food protein-induced enterocolitis syndrome among children in northern Sweden-A retrospective review from 2004-2018.

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.

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.

Outpatient Botulinum Injections for Early Obstructive Symptoms in Patients with Hirschsprung Disease.

INTRODUCTION: Botulinum toxin (BT) injections may play a role in preventing Hirschsprung associated enterocolitis (HAEC) episodes related to internal anal sphincter (IAS dysfunction). Our aim was to determine the association of outpatient BT injections for early obstructive symptoms on the development of HAEC. METHODS: A retrospective review of children who underwent definitive surgery for Hirschsprung disease (HSCR) from July 2010 - July 2020 was performed. The timing from pull-through to first HAEC episode and to first BT injection was recorded. Primary analysis focused on the rate of HAEC episodes and timing between episodes in patients who did and did not receive BT injections. RESULTS: Eighty patients were included. Sixty patients (75%) were male, 15 (19%) were diagnosed with trisomy 21, and 58 (72.5%) had short-segment disease. The median time to pull-through was 150 days (IQR 16, 132). Eight patients (10%) had neither an episode of HAEC or BT injections and were not included in further analysis. Forty-six patients (64%) experienced at least one episode of HAEC, while 64 patients (89%) had at least one outpatient BT injection. Compared to patients who never received BT injections (n = 9) and those who developed HAEC prior to BT injections (n = 35), significantly fewer patients who received BT injections first (n = 28) developed enterocolitis (P < 0.001), with no patient developing more than one HAEC episode. CONCLUSION: Outpatient BT is associated with decreased episodes of HAEC and increased interval between HAEC episodes requiring inpatient treatment. Scheduling outpatient BT injections to manage obstructive symptoms may be beneficial after pull-through for HSCR.

The impact of the COVID-19 pandemic on other infections differs by their route of transmission: A retrospective, observational study in Japan.

INTRODUCTION: The Coronavirus disease 2019 (COVID-19) pandemic and people's subsequent behavioral changes have decreased the cases of respiratory infection worldwide. However, research on infectious diseases with other transmission modes is insufficient. The aim was to assess the impact of the COVID-19 pandemic on non-respiratory infectious diseases: infectious enterocolitis, sexually transmitted diseases such as human immunodeficiency virus (HIV) infection and syphilis, and tick-borne diseases. METHODS: This retrospective, cohort study used comprehensive surveillance data from the National Institute of Infectious Diseases in Japan from January 1, 2018, to December 31, 2021. The number of cases of infectious diseases before the COVID-19 pandemic (2018-2019) was compared with that during the COVID-19 pandemic (2020-2021). Reduction rates were calculated as the number of disease cases during the COVID-19 pandemic in 2020 and 2021, respectively, divided by the mean number of disease cases in 2018 and 2019. RESULTS: The total numbers of cases of infectious enterocolitis, sexually transmitted diseases, and tick-borne diseases during the study period were 2,507,304 cases, 24,972 cases, and 3012 cases, respectively. The number of cases decreased for infectious enterocolitis and sexually transmitted diseases during the COVID-19 pandemic compared with before the COVID-19 pandemic, with an approximately 40-50% decrease in enterocolitis and 30-55% decreases in sexually transmitted diseases. However, cases of tick-borne diseases changed little, with a 0.2% increase in 2020 and a 6% increase in 2021. CONCLUSION: The COVID-19 pandemic had a different impact on the number of cases of infectious diseases depending on their mode of transmission.

Low incidence of colonic complications after severe Shiga toxin-producing E. coli O104:H4 infection.

BACKGROUND: In summer 2011, Shiga toxin producing Escherichia coli (EHEC) serotype O104:H4 caused the most severe EHEC outbreak in Germany to date. The case of a previously recovered patient with symptomatic postinflammatory colonic stenosis following EHEC- infection prompted us to conduct a prospective study to assess the macro- and microscopic intestinal long-term damage in a cohort of patients who had suffered from severe EHEC colitis. METHODS: Following EHEC infection in 2011, 182 patients were offered to participate in this study between January 2013 and October 2014 as part of the post-inpatient follow-up care at the University Medical Center Hamburg-Eppendorf and to undergo colonoscopy with stepwise biopsies. Prior to colonoscopy, medical history and persistent post-infectious complaints were assessed. RESULTS: Out of 182 patients, 22 (12%) participated in the study, 18 (82%) were female. All patients had been hospitalized due severe EHEC enterocolitis: 20 patients (90%) had subsequently developed hemolytic uremic syndrome (HUS), 16 patients (72%) had additionally required dialysis. On assessment prior to colonoscopy, all patients denied any abdominal complaints before EHEC-infection but 8 (36%) patients reported persistent post-infectious symptoms. According to the ROME IV criteria, 4 (18%) patients met the definition for post-infectious irritable bowel syndrome (PI-IBS). In all patients with persistent symptoms, colonoscopies and histological examination were unremarkable. Only in one symptom-free patient, biopsy revealed a locally limited cryptitis of the caecum, while all patients without complaints had inconspicuous histological and endoscopical findings. CONCLUSION: Following infection colonic stenosis is a serious but rare long-term complication in patients who had suffered from severe enterocolitis. However, a significant proportion of these patients develop PI-IBS.

Prevalence of Hirschsprung-associated enterocolitis in patients with Hirschsprung disease.

PURPOSE: Hirschsprung's associated enterocolitis (HAEC) is a complication of Hirschsprung's Disease (HD) with considerable morbidity and mortality. The variability in presentation leads to a wide variety of the reported prevalence pre-and postoperatively. This systematic review aimed to clarify the prevalence of HAEC in short-(S-HD), long (L-HD), TCA and the type of operation used. METHODS: A systematic literature-based search for relevant cohorts was performed using Pubmed/Medline, Cochrane Library from its inception to May 2021. Studies reporting on pre-and postoperative enterocolitis, segment length, and surgical procedure (Soave, Swenson, Duhamel) were included. Pooled prevalence and subgroup analysis have been calculated for pre-and postoperative HAEC. RESULTS: 4738 articles were identified from the literature search, among which 57 studies, including 9744 preoperative and 8568 postoperative patients, were included. The groups were sorted by length of the aganglionic segment for further analysis. The pooled prevalence for preoperative HAEC was 18.3% for all types, 15.2% for S-HD and 26.1% for TCA. The pooled prevalence for postoperative HAEC was in total 18.2% for all segment lengths and used techniques. Subgroup analysis showed no significant difference in the occurrence of postoperative enterocolitis between the three techniques. CONCLUSION: The prevalence of preoperative HAEC increases with segment length. However, pooled data suggest that the postoperative risk for developing HAEC, independently of the employed method and segment length, is comparable to the preoperative risk.

Disease Course and Treatment Response of Eosinophilic Gastrointestinal Diseases in Children With Liver Transplantation: Long-Term Follow-Up.

INTRODUCTION: To describe the clinical and laboratory profile, natural course, treatment outcome, and risk factors of posttransplant esophageal and nonesophageal eosinophilic gastrointestinal disorders (EGIDs). METHODS: All children (aged <18 years) who underwent liver transplantation, between 2011 and 2019, in a single transplant center with a follow-up period of 1 year or more posttransplant and with a history of posttransplant endoscopic evaluation were included in this study. RESULTS: During the study period, 89 children met the inclusion criteria. Patients were followed for a median of 8.0 years. A total of 39 (44%) patients were diagnosed with EGID after transplantation. Of these, 29 (33%) had eosinophilic esophagitis (EoE), and 10 (11%) had eosinophilic gastritis, gastroenteritis or enterocolitis. In comparison with the non-EGID group, patients with EGID were younger at transplant (P ≤ 0.0001), transplanted more frequently due to biliary atresia (P ≤ 0.0001), and had higher rates of pretransplant allergy (P = 0.019). In the posttransplant period, they had higher rates of mammalian Target of Rapamycin inhibitor use (P = 0.006), Epstein-Barr virus viremia (P = 0.03), post-transplant lymphoproliferative disease (P = 0.005), and allergen sensitization (P ≤ 0.0001). In regression analysis, young age at transplant, age at diagnosis, pretransplant atopic dermatitis, and post-transplant lymphoproliferative disease were associated with an increased risk of EGID or EoE. Laboratory abnormalities such as anemia (P = 0.007), thrombocytosis (P = 0.012), and hypoalbuminemia (P = 0.031) were more commonly observed in the eosinophilic gastritis, gastroenteritis or enterocolitis group than in the EoE group. Following treatment, most patients had symptomatic resolution at 3 months and histologic resolution at 6 months postdiagnosis. Among the patients who had 5 years of follow-up, none recurred. DISCUSSION: EGID is a common posttransplant diagnosis, which seems to affect patients who are transplanted earlier and who have pretransplant atopy. Posttransplant EGID is responsive to treatment, but as histologic remission occurs after symptomatic resolution, the decision to perform control endoscopy should be delayed.

Clinical presentation and management of food protein-induced enterocolitis syndrome in 113 Swedish children.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy causing severe acute gastrointestinal symptoms and lethargy, mainly affecting infants and young children. There are geographic variations in its clinical features. This study aimed to describe the clinical characteristics and management of FPIES in Swedish children. METHODS: The study included children who presented with acute FPIES during 2008-2017. All Swedish pediatric departments (n = 32) were invited to report their known patients. Data were collected through chart reviews and interviews with parents. RESULTS: Eighteen pediatric departments contributed, and 113 patients were included. Most had a family history of atopy (74%), and 51% had an atopic disease. Common trigger foods were cow's milk (26%), fish (25%), oat (22%), and rice (8%). Most patients (85%) reacted to a single food. The median age at first reaction was 3.9 months for cow's milk and 6.0 months for other foods (p < 0.001, range 1.0 month to 9 years). Repetitive vomiting (100%), lethargy (86%), and pallor (61%) were common symptoms; 40% had diarrhea. Sixty percent visited the emergency department, and 27% of all patients were hospitalized. Most patients were diagnosed clinically (81%). Specific IgE for the trigger food was positive in 4/89 tested patients (4%), and skin prick test for the trigger food was positive in 1/53 tested patients (2%). CONCLUSIONS: In our Swedish study of 113 children, cow's milk, fish, and oat were the commonest trigger foods. Most patients reacted to a single food, and IgE sensitization was rare.

Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer.

OBJECTIVE: This phase II clinical trial evaluated the safety and antitumor activity of balstilimab, an anti-PD-1 antibody, in patients with previously-treated, recurrent/metastatic cervical cancer. METHODS: Eligible patients were 18 years or older with recurrent and/or metastatic cervical cancer and who had relapsed after a prior platinum-based treatment regimen for advanced disease. Balstilimab was administered intravenously at 3 mg/kg once every two weeks, for up to 24 months. The primary endpoint was objective response rate (ORR, RECIST v1.1) as assessed by an independent review committee. RESULTS: At data cutoff, 161 women (median age, 53 years [range 25-81]) were enrolled and treated with balstilimab. Of these, 140 had measurable disease at baseline and one prior line of platinum-based therapy in the metastatic, persistent, or recurrent setting; these patients were included in the efficacy analyses. The ORR was 15% (95% CI, 10.0%-21.8%) and included 5 patients with a complete response and 16 with a partial response. The median duration of response was 15.4 months. In patients with PD-L1-positive tumors the ORR was 20%, however patients with PD-L1-negative tumors also responded to balstilimab (ORR, 7.9%). Responses were not restricted to tumors of squamous cell histology, and an ORR of 12.5% was seen in the subset of patients with cervical adenocarcinoma. The disease control rate was 49.3% (95% CI, 41.1%-57.5%). Immune-mediated enterocolitis (3.1%) and diarrhea (1.9%) were the most common grade 3 or higher treatment-related adverse events. CONCLUSION: Balstilimab demonstrated meaningful and durable clinical activity, with manageable safety, in patients with previously-treated, recurrent/metastatic cervical cancer.

An exploration of factors associated with food protein-induced enterocolitis syndrome: Birth, infant feeding and food triggers.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergic disorder with a well-characterized phenotype, but limited understanding of factors associated with food cross-reactivity, severity and tolerance. METHODS: A retrospective cohort study spanning 20 years on children with acute FPIES from a single paediatric tertiary centre in New South Wales, Australia, focusing on identifying food trigger co-associations and factors associated with reaction severity, multiple trigger FPIES and/or tolerance was performed. RESULTS: A total of 168 individuals with 329 recorded FPIES episodes between 1997 and 2017 were included. 49% were male. The median age at first reaction was 5 months, and median age at diagnosis was 9 months. 73% experienced at least one severe FPIES reaction. Rice (45%), cow's milk (30%) and soya (13%) were the most common triggers. Rice or cow's milk FPIES was strongly associated with increased odds of having multiple trigger FPIES. The odds of having multiple food FPIES and severe reactions were slightly decreased with vaginal delivery. No factors were associated with increased risk of severe reactions. Infants with rice and grains FPIES outgrew their reactions at an earlier age, compared to those with fish FPIES. CONCLUSIONS: Rice remains the most common trigger in Australia with co-associations between rice/oats and cow's milk/soya observed. This suggests that taxonomically related foods may share similar protein structure and trigger similar mechanisms of antigen recognition. Vaginal delivery may have a mild protective effect on the development of multiple FPIES and severe reactions. No other features from birth or infant-feeding history influenced outcomes in FPIES.

Reducing Underdiagnosis of Hirschsprung-Associated Enterocolitis: A Novel Scoring System.

BACKGROUND: Hirschsprung-Associated Enterocolitis (HAEC) is a life-threatening and difficult to diagnose complication of Hirschsprung Disease (HSCR). The goal of this study was to evaluate existing HAEC scoring systems and develop a new scoring system. METHODS: Retrospective, multi-institutional data collection was performed. For each patient, all encounters were analyzed. Data included demographics, symptomatology, laboratory and radiographic findings, and treatments received. A "true" diagnosis of HAEC was defined as receipt of treatment with rectal irrigations, antibiotics, and bowel rest. The Pastor and Frykman scoring systems were evaluated for sensitivity/specificity and univariate and multivariate logistic regression performed to create a new scoring system. RESULTS: Four centers worldwide provided data on 200 patients with 1450 encounters and 369 HAEC episodes. Fifty-seven percent of patients experienced one or more episodes of HAEC. Long-segment colonic disease was associated with a higher risk of HAEC on univariate analysis (OR 1.92, 95% CI 1.43-2.57). Six variables were significantly associated with HAEC on multivariate analysis. Using published diagnostic cutoffs, sensitivity/specificity for existing systems were found to be 38.2%/96% for Pastor's and 56.4%/86.9% for Frykman's score. A new scoring system with a sensitivity/specificity of 67.8%/87.9% was created by stepwise multivariate analysis. The new score outperformed the existing scores by decreasing underdiagnosis in this patient cohort. CONCLUSIONS: Existing scoring systems perform poorly in identifying episodes of HAEC, resulting in significant underdiagnosis. The proposed scoring system may be better at identifying those underdiagnosed in the clinical setting. Head-to-head comparison of HAEC scoring systems using prospective data collection may be beneficial to achieve standardization in the field.

Food protein-induced enterocolitis syndrome epidemiology.

OBJECTIVE: Food protein-induced enterocolitis syndrome (FPIES) is a condition with heterogeneous features (ie, age at presentation, severity, food triggers, comorbidities) and is not as rare as initially believed. In the last few years, the first population-based epidemiologic study, few prospective birth cohort evaluating FPIES prevalence, and several larger (>100 patients) studies have been published, making epidemiologic estimation more reliable. In this review, we report on the available data on the epidemiology of FPIES. DATA SOURCES: PubMed review using the following words: FPIES, epidemiology, and prevalence. STUDY SELECTIONS: The review focused on the population-based epidemiologic study, few prospective birth cohort evaluating FPIES prevalence, and several larger (>100 patients) studies. RESULTS: We identified 8 population or cohort studies. CONCLUSION: FPIES is not rare in both children and adults and may affect as many as 900,000 people in the United States alone. Most children and adult with FPIES seem to react to 1 to 2 foods; however, they may need further diet restriction owing to high level of comorbidity with immunoglobulin E-mediated food allergies and eosinophilic esophagitis. Globally, cow's milk, rice/oat, and seafood seem to be the most common triggers.

Food protein-induced enterocolitis syndrome: Current practices in oral food challenge.

Background: Oral food challenges (OFC) in food protein-induced enterocolitis syndrome (FPIES) are performed to confirm a diagnosis, test for development of tolerance, and find safe alternatives. Objective: We aimed to define OFC outcomes and identify safer test strategies. Methods: OFCs performed in children with FPIES over a 5-year period were reviewed. Results: A total of 160 OFCs were performed in 59 children (median age, 2.3 years). The most commonly tested foods were hen's egg, fish, and cow's milk. Sixty-six OFC results (41.3%) were positive. Twelve (18.2%) reactions were mild, 18 (27.3%) were moderate, and 36 (54.5%) were severe. Intravenous fluid, ondansetron, and corticosteroids were administered in 83.3, 72.7, and 66.7% of the patients, respectively; one patient required hospitalization. A reaction was most likely with fish (odds ratio [OR] 2.878 [95% confidence interval {CI}, 1.279-6.473]; p = 0.011), and least likely with cow's milk (OR 0.268 [95% CI, 0.082-0.872]; p = 0.029). Of the 36 OFCs with egg yolk, 23 patients had a failed OFC, and of the 17 OFCs with egg white (all tolerant to egg yolk), only 2 patients had a failed result. Interestingly, two patients tolerated baked whole egg but not egg yolk. In cow's milk FPIES, two patients could consume fermented milk but not fresh milk. Of the 11 patients with anchovy-triggered FPIES, 6 tolerated sea bass, and 5 tolerated trout, whereas 4 patients with sea bass FPIES tolerated trout. Conclusion: The search for alternative food species, processing, or subdivision of a trigger food is common practice in FPIES, which reflects the expectations of children and their families. The experience gained can be put into practice and will contribute to the understanding of the disease mechanism.

The impact of botulinum injection for hospitalized children with Hirschsprung-associated enterocolitis.

INTRODUCTION: Stasis from obstruction at the level of the internal anal sphincter (IAS) can lead to Hirschsprung-associated enterocolitis (HAEC) and may be improved by botulinum toxin (BT) injections. Our aim was to determine if BT injection during HAEC episodes decreased the number of recurrent HAEC episodes and/or increased the interval between readmissions. METHODS: A retrospective review was performed of patients admitted for HAEC from January 2010 to December 2019. Demographics and outcomes of patients who received BT were compared to patients who did not receive BT during their hospital stay. RESULTS: A total of 120 episodes of HAEC occurred in 40 patients; 30 patients (75%) were male, 7 (18%) had Trisomy 21 and 10 (25%) had long-segment disease. On multivariate analysis, patients who received BT during their inpatient HAEC episode had a longer median time between readmissions (p = 0.04) and trending toward an association with fewer readmissions prior to a follow-up clinic visit (p = 0.08). CONCLUSION: The use of BT in HD patients hospitalized for HAEC is associated with an increased time between recurrent HAEC episodes and trended toward fewer recurrent episodes. The use of BT should be considered in the management of patients admitted with HAEC.