Faculty Bibliography

BACKGROUND:Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by profuse vomiting within hours of ingestion of the causative food. We have previously reported that FPIES is associated with systemic innate immune activation in the absence of a detectable antigen-specific antibody or T-cell response. The mechanism of specific food recognition by the immune system remains unclear. OBJECTIVE:Our aim was to identify immune mechanisms underlying FPIES reactions by proteomic and flow cytometric analysis of peripheral blood. METHODS:Children with a history of FPIES underwent supervised oral food challenge. Blood samples were taken at baseline, at symptom onset, and 4 hours after symptom onset. We analyzed samples from 23 children (11 reactors and 12 outgrown). A total of 184 protein markers were analyzed by proximity ligation assay and verified by multiplex immunoassay. Analysis of cell subset activation was performed by mass cytometry and spectral cytometry. RESULTS:17 cells. CONCLUSIONS:These results demonstrate a unique IL-17 signature and activation of innate lymphocytes in FPIES.

RATIONALE/BACKGROUND:We recently showed that multicomponent traditional Chinese medicine (TCM) therapy had steroid-sparing effects in moderate-to-severe eczema. We sought to evaluate TCM effects in severe eczema in a 7-year-old male with refractory disease and corticosteroid withdrawal syndrome. METHODS:Prior to referral, the patient had been treated since infancy with increasingly intensive standard of care, including high-dose topical and systemic corticosteroid and antibiotic therapy and was unable to tolerate further steroid treatment. The patient was administered a combination of oral and topical TCM for 17 months following discontinuation of his steroid regimen. His overall medical condition was assessed by SCORAD criteria and laboratory evaluations of serum IgE, absolute eosinophil count, and liver and kidney function tests. RESULTS:The patient showed rapid improvement of clinical measures of disease after starting TCM therapy, with marked improvement of sleep quality within the first week, complete resolution of itching, oozing, and erythema at 2 weeks, and a 79% and 99% decrease in his SCORAD values after one month and 3-6 months of TCM, respectively. Serum total IgE decreased by 75% (from 19,000 to 4630 (kIU/L), and absolute eosinophil counts decreased by 60% (from 1000 to 427 cells/μL) after 12 months of treatment. The patient did not require oral or topical steroids during the 17-month trial of TCM. TCM was tapered without complications. His dermatologic manifestations continued to be well-controlled 3 months after discontinuation. CONCLUSION/CONCLUSIONS:This case study suggests TCM should be further evaluated in controlled clinical studies of patients with severe, refractory eczema and steroid withdrawal syndrome.

PURPOSE OF REVIEW/OBJECTIVE:The prevalence of food allergy is increasing on a global scale, and therefore increased attention is being paid to specific food allergy epidemiology and management. There has been a large amount of progress made in the last decade on human trials of wheat oral immunotherapy (WOIT). RECENT FINDINGS/RESULTS:To date, there has been one multicenter, double-blind, randomized controlled trial of WOIT, one randomized, noncontrolled trial of WOIT, and several smaller, nonrandomized clinical trials of WOIT. WOIT trials are generally limited by smaller sample sizes, affecting the demographic skew of evaluated patients. In addition, there is minimal standardization of efficacy and safety outcomes between trial protocols, making head-to-head comparison challenging. However, some common themes emerge. The majority of WOIT regimens result in successful desensitization, and success is more likely with higher maintenance dosing for longer periods of time. Limited studies have looked at sustained unresponsiveness in WOIT. WOIT can induce allergic reactions, including anaphylaxis, but more severe reactions often have an associated augmenting factor, such as exercise. Lower maintenance doses likely are associated with less severe reactions, and food modification and/or adjunct therapeutics may also decrease the risk of reactions. SUMMARY/CONCLUSIONS:WOIT trials are ongoing and will optimize updosing protocols and maintenance doses to improve efficacy and safety.

OBJECTIVE:Food protein-induced enterocolitis syndrome (FPIES) is typically diagnosed based on a characteristic clinical history; however, an oral food challenge (OFC) may be necessary to confirm the diagnosis or evaluate for the development of tolerance. FPIES OFC methods vary globally, and there is no universally agreed upon protocol. The objective of this review is to summarize reported FPIES OFC approaches and consider unmet needs in diagnosing and managing FPIES. DATA SOURCES:PubMed database was searched using the keywords food protein-induced enterocolitis syndrome, oral food challenge, cow milk allergy, food allergy, non-immunoglobulin E-mediated food allergy and FPIES. STUDY SELECTIONS:Primary and review articles were selected based on relevance to the diagnosis of FPIES and the FPIES OFC. RESULTS:We reviewed the history of FPIES and the evolution and variations in the FPIES OFC. A summary of current literature suggests that most patients with FPIES will react with 25% to 33% of a standard serving of the challenged food, there is little benefit to offering a divided dose challenge unless there is suspicion of specific immunoglobulin E to the food being challenged, reactions typically appear within 1 to 4 hours of ingestion, and reactions during OFC rarely result in emergency department or intensive care unit admission. CONCLUSION:International standardization in the FPIES OFC approach is necessary with particular attention to specific dose administration across challenged foods, timing between the patient's reaction and offered OFC to verify tolerance, patient safety considerations before the OFC, and identification of characteristics that would indicate home reintroduction is appropriate.

BACKGROUND:Guidelines on the early introduction of allergen-containing foods are evolving; however, little national data exist defining current allergen-feeding practices. OBJECTIVE:To investigate the consumption rates of foods containing egg and peanut among infants and toddlers before the guideline changes in 2017. METHODS:The Feeding Infants and Toddlers Study 2016 was conducted nationally among 3235 caregivers with a child under 4 years of age. The 24-hour dietary recalls were reviewed for peanut or egg ingredients. Participants were categorized as "consuming peanut or egg-containing foods" or "not consuming peanut or egg-containing foods." Data on physician-diagnosed food allergies and avoidance were collected. RESULTS:The consumption rates of peanut- and egg-containing foods were low. For the age group of 4 to 5.9 months, 0.3% reported peanut consumption and 2.4% reported egg consumption. For the age group of 6 to 8.9 months, 0.9% reported eating peanut-containing foods and 13.0% egg, and for the age group of 9 to 11.9 months, 5.5% were consuming peanut-containing foods and 33.2% egg-containing foods. Peanut or egg ingredients were identified in the diet of children whose caregivers reported avoidance. CONCLUSION/CONCLUSIONS:Before the publication of the 2017 Addendum Guidelines for the Prevention of Peanut Allergy, there were low rates of reported peanut consumption across the study population with less than 1% of any age group before 9 months of age and less than 6% in any age group before 12 months of age consuming peanut on the 24-hour recall day. In addition, reported egg consumption was low and increased with age. These results serve as an important baseline comparison for future studies evaluating the implementation and impact of early peanut and egg introduction.

OBJECTIVE:Although food protein-induced enterocolitis syndrome (FPIES) was first described approximately 50 years ago and research is increasing, there are still considerable unmet needs in FPIES. This article catalogs the areas of progress and areas for further research. DATA SOURCES/METHODS:Through our personal experiences in caring for patients with FPIES, our personal research, and a review of the existing FPIES literature as indexed in PubMed, we explored what is known and what is needed in FPIES. STUDY SELECTIONS/METHODS:The studies that have improved the knowledge of FPIES, defined phenotypes, allowed for better-informed management of FPIES, and laid the groundwork for further research. RESULTS:Further research is needed in the areas of prevalence, natural history, trigger foods, threshold doses, how and when to perform oral food challenges, and immunopathogenesis of this disorder. Development of a biomarker and determination of the best method to treat reactions is also needed. Furthermore, FPIES has a substantial psychosocial and economic impact on families, and more research is needed in developing and implementing ameliorating strategies. CONCLUSION/CONCLUSIONS:By partnering together, health care providers, advocacy organizations, and families can continue to advance our understanding and improve the care of patients and families living with FPIES.

BACKGROUND/UNASSIGNED:Chronic food protein-induced enterocolitis syndrome (FPIES) is a cell-mediated gastrointestinal food hypersensitivity described almost exclusively in infants fed cow's milk or soy formula. A timely diagnosis is challenging due to a number of factors, including broad differential diagnoses, absence of specific biomarkers, and delayed symptom onset. OBJECTIVE/UNASSIGNED:This report aimed to highlight how the severity of presentation can further impede a timely diagnosis in chronic FPIES. Methods: A case of presumed chronic FPIES to soy with previously unreported complications of intracranial hemorrhage and cerebral venous sinus thrombosis was described. RESULTS/UNASSIGNED:We reported a case of a female infant fed a soy formula who presented during the third week of life with intermittent and progressive emesis, diarrhea, and lethargy, which culminated in severe dehydration, with early hospital course complications of seizures, intracranial hemorrhage, and cerebral venous sinus thrombosis. Although not recognized until weeks into the hospital course, many of the presenting symptoms and laboratory abnormalities were characteristic of chronic FPIES. An ultimate consideration of FPIES led to transition to amino acid-based formula and gradual resolution of gastrointestinal symptoms. Close outpatient follow-up was essential in facilitating subsequent age-appropriate solid food introduction. CONCLUSION/UNASSIGNED:The severity of presentation in FPIES can represent an additional barrier to a timely diagnosis. Early consideration of this entity in the differential diagnosis of patients with typical FPIES features, regardless of the additional presence of atypical and severe complications, may help with more timely recognition and intervention. In addition, there is an increased need for close follow-up as an outpatient in severe FPIES cases.