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Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy diagnosed via history and/or an oral food challenge (OFC)., Objective: To determine allergists' approach to FPIES OFCs., Methods: A web-based survey was e-mailed to 1100 randomly selected American Academy of Allergy, Asthma and Immunology members., Results: A total of 132 individuals responded (12% response rate). A total of 95.5% (n = 105) of respondents perform OFCs in their practice, but only 58.7% (n = 71) perform FPIES OFCs. The median number of FPIES OFCs in children was reported as 3 per year (range, 0-76); all but 1 respondent (2.5%) had not performed any FPIES OFCs in adults. The most common FPIES OFC foods were cow's milk, rice, lightly cooked egg, oat, soy, baked milk, and baked egg. The decision to offer FPIES OFCs was based on the severity of past reactions, the patient and family's desire, and the patient's age. FPIES OFCs were most commonly performed in an outpatient setting, with placement of peripheral intravenous access depending on the severity of past reactions and with a serving appropriate for age divided into 3 equal portions administered over 30 minutes. There was significant variability in the approach to conducting FPIES OFCs. Most respondents (87.4%, n = 127) indicated that specific guidelines for performing FPIES OFCs would be helpful., Conclusions: Our study highlights the discordance in allergists' practices performing OFCs for IgE-mediated food allergy compared with FPIES. The lack of universal agreement on the optimal way to perform OFCs in FPIES demonstrates the need for future studies to develop a standardized protocol for FPIES OFCs., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021. Published by Elsevier Inc.)

Food protein-induced enterocolitis syndrome is still a mysterious disease, pathogenically poorly characterized, although the first FPIES case has been described in 1967. Mainly, food protein-induced enterocolitis syndrome diagnosis is based on clinical history. The oral food challenge remains the gold standard to confirm the diagnosis, especially in particular situations. Although there are no diagnostic laboratory or imaging tests which are specific for diagnosis, they could, however, sometimes be helpful to rule out clinical conditions which are similar to food protein-induced enterocolitis syndrome reactions. The purpose of this review is to define the clinical features of FPIES and to summarize the current available tools for the diagnosis of FPIES. This review is intended to be a practical guide for the clinician facing a patient with food protein-induced enterocolitis syndrome avoiding delayed diagnosis with unnecessary laboratory tests and detrimental treatments. Moreover, it highlights the unmet needs in diagnosis that require urgent attention from the scientific community to improve the management of patients with FPIES., (© 2020 John Wiley & Sons Ltd.)

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. Its relationship to the major atopic manifestations (atopic dermatitis [AD], IgE-mediated food allergy [IgE-FA], allergic rhinitis [AR], asthma) is not understood., Objective: To determine the clinical characteristics, epidemiologic features, and natural history of FPIES in relation to the major atopic manifestations., Methods: We examined our primary care birth cohort of 158,510 pediatric patients, of whom 214 patients met 2017 FPIES diagnostic criteria. We measured the influence of FPIES on developing subsequent atopic disease., Results: Pediatric FPIES incidence was between 0.17% and 0.42% depending on birth year. As in prior reports, most patients had an acute presentation (78%), and milk, soy, oat, rice, potato, and egg were common triggers. The mean age of diagnosis was 6.8 months. Atopic comorbidity was higher in patients with FPIES compared with healthy children (AD, 20.6% vs 11.7%; IgE-FA, 23.8% vs 4.0%; asthma, 26.6% vs 18.4%; AR, 28.0% vs 16.7%; P < .001 χ 2 ). However, longitudinal analyses indicated that prior FPIES did not influence the rate of atopy development., Conclusions: The incidence of FPIES in our cohort was initially low, but is increasing. Food allergen distribution, presentation, and age of onset are similar to prior reports. Patients with FPIES have high rates of atopic comorbidity. However, longitudinal analysis does not support direct causation as the etiology of these associations. Rather it suggests a shared predisposition to both types of allergy, or associative bias effects. This work refines our understanding of the natural history of FPIES by elucidating associations between FPIES and atopy., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Oral food challenges are an integral part of an allergist's practice and are used to evaluate the presence or absence of allergic reactivity to foods. A work group within the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology was formed to update a previously published oral food challenge report. The intention of this document was to supplement the previous publication with additional focus on safety, treatment of IgE-mediated allergic reactions, guidance for challenges in infants and adults, psychosocial considerations for children and families participating in an oral food challenge, specific guidance for baked milk or baked egg challenges, masking agents and validated blinding recipes for common food allergens, and recommendations for conducting and interpreting challenges in patients with suspected food protein-induced enterocolitis syndrome. Tables and figures within the report and an extensive online appendix detail age-specific portion sizes, appropriate timing for antihistamine discontinuation, serum and skin test result interpretation, written consents, and instructional handouts that may be used in clinical practice., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergic disorder that has gained a major interest the past decade. FPIES prevalence, which still needs to be accurately determine in different populations, appears to be higher than previously thought (ie up to 0.7% in infants in the 1st year of life). FPIES to seafood in adults is also increasingly reported; limited data suggest that adult FPIES is most commonly triggered by shellfish, tends to affect females more than men, is characterized by a significant delay in diagnosis and a prolonged course. The first international consensus guidelines on diagnosis and management of FPIES have been published in 2017, proposing new diagnostic criteria as well as new criteria for a positive oral food challenge. However, there is a need to develop new biomarkers to improve the diagnosis and management of FPIES patients, and this requires a better understanding of the pathophysiology. Recently, the role of T cells has been questioned and a major role of innate immune cells has been suggested in acute FPIES. Regarding the treatment of acute FPIES reaction, ondansetron has emerged as an adjunct to intravenous rehydration in moderate-severe reactions and as a first-line treatment in mild reactions. Important information regarding the nutritional management of FPIES patients that might be complex has also been provided in the international guidelines. In this review, we discuss recent advances regarding all those different aspects., (© 2019 John Wiley & Sons Ltd.)

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that is diagnosed based on clinical findings, but can be confirmed with oral food challenge (OFC). OFC is more often performed to assess the development of tolerance. Most studies describing OFCs in FPIES are limited in size., Objective: We sought to describe our experience with OFCs using our FPIES protocol. Patients were given one-third of serving size with a 4-hour observation period, followed by home titration to full dose., Methods: We conducted a retrospective chart review of patients who underwent OFC via the FPIES protocol from 2014 to 2017. Data regarding the history of reaction, age at the time of challenge, and reactions during challenge or with home introduction were collected., Results: A total of 169 OFCs were completed under the FPIES protocol, in 119 patients to 19 different foods. Thirty challenges (18%) were positive, with 17 challenges (10%) during initial challenge and 13 (7.7%) during home dosing. Most reactions during initial challenge required intravenous fluids (IVF), but hypotension was uncommon. One hundred thirty-nine (82%) OFCs were negative with home introduction, indicating tolerance to the challenged foods. The mean age of passing a challenge to milk, soy, and grain was earlier than that of other solid foods., Conclusions: Our data suggest that our FPIES OFC protocol is safe. Early administration of IVF may prevent the development of hypotension. It is difficult to stratify the risk of severe or delayed reaction based on patient characteristics, and more data are needed to identify those appropriate for home introduction., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: An increasing number of infants are diagnosed with food protein-induced enterocolitis syndrome (FPIES), a non-IgE-mediated food allergy. Until now, T-cell, food-specific mechanisms have been hypothesized., Methods: Sixteen children (11M, 5F), affected by FPIES from cow's milk, wheat, fruit, rice, and others, experienced 25 acute episodes managed at our emergency department (ED) and eight FPIES reactions during oral food challenges (OFC). We compared the laboratory data in resting conditions, in the absence of infectious diseases, with data collected during the 25 acute ED episodes (blood samples drawn at 2-12 hours) and the eight positive OFCs (three samples at 2, 6, and 12 hours). The onset of symptoms was used as a reference time point., Results: In basal conditions, total IgE, WBC, neutrophil and eosinophil count, CRP, and SGPT were found normal. LDH and SGOT values were high (627.81±97.88 and 45.75±10.26 UI/L, respectively). During ED reactions, LDH and SGOT increased to 794.21±247.28 (P=.028) and 51.08±16.99 UI/L (P=.14) and neutrophils count and CRP to 8.44±3.82×10 3 /μL (P=.0009) and 3.27±5.73 mg/dL (P=.0014), respectively. During positive OFC, LDH and SGOT did not vary significantly; CRP increased from 0.14±0.18 to 2.49±3.65 mg/dL (P=.00189) and neutrophil count from 2.79±1.42 to 7.10±3.98×10 3 /μL (P=.00096)., Conclusions: FPIES reactions are characterized by neutrophilia and by a time-dependent, significant increase in CRP, indicating that inflammatory mechanisms are in place. This suggests new directions for research on FPIES pathogenesis., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Food protein-induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Food protein-induced enterocolitis (FPIES) is a rare non-IgE mediated disease. Most studies have been limited in nature, with the largest cohort being 66 patients. The most common foods that have been reported are milk and soy., Objective: A retrospective chart review of patients seen in the Allergy Section at The Children's Hospital of Philadelphia with International Classification of Diseases Ninth Revision code of 558.3 (Allergic Gastroenteritis and Colitis) between 2007 and 2012 was conducted to identify patients with suspected FPIES. Diagnosis of FPIES was confirmed based on meeting clinical criteria of delayed reaction with pronounced vomiting and/or diarrhea. Data regarding patient characteristics and features of their reactions were collected for analysis and comparison with existing studies., Results: A total of 462 cases were identified in our chart review. Patients had a similar demographic profile to the normal allergy patients seen in our clinic. The most common foods identified were milk (67%), soy (41%), rice (19%), oat (16%), and egg (11%). Patients had onset of FPIES to milk and soy around 7 months of age compared with 12 months of age for solid foods. FPIES reactions were identified to meats, tree nuts, peanuts, fruits, and vegetables; 70% of the patients reacted to one or two foods. Skin prick testing and atopy patch testing were not helpful in identifying the foods., Conclusion: FPIES reactions were seen more frequently than previously described. However, the presentation and clinical features were similar to previous reports. Milk- and soy-triggered FPIES were common, and 43.5% of patients who had a milk trigger reacted to soy. There is no laboratory test to identify foods that cause FPIES, and clinician-supervised oral food challenge is the only definitive test available., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)