Faculty Bibliography

CME EDUCATIONAL OBJECTIVES 1. Recognize manifestations, diagnosis, and management of food protein-induced enterocolitis syndrome (FPIES) in an outpatient setting. 2. Assess nutritional needs and provide anticipatory guidance for dietary management. 3. Recognize the indications of when to refer for assessment of resolution of FPIES using physician-supervised food challenges. Food protein-induced enterocolitis syndrome (FPIES) is an under-recognized non-immunoglobulin E (IgE)-mediated gastrointestinal food allergy affecting primarily infants and toddlers. An abnormal response to food antigen resulting in local inflammation is thought to lead to increased intestinal permeability and fluid shift. The primary features of acute FPIES are repetitive, projectile vomiting, lethargy, pallor, diarrhea, and dehydration. Chronic FPIES is typically seen in young infants with continued exposure to cow's milk or soy-based formula. Biomarkers are lacking and patients may undergo extensive workups for their symptoms, which often leads to a delay in diagnosis and puts infants at risk for feeding difficulties, nutritional deficiencies, and failure to thrive. This review will provide a guide in how to recognize the clinical features of and manage FPIES.

Although the need for nutritional and dietary intervention is a common thread in food allergy management, the type of food allergic disorder and the identified food allergen will influence the approach to dietary intervention. A comprehensive nutrition assessment with appropriate intervention is warranted in all children with food allergies to meet nutrient needs and optimize growth. However, dietary elimination in food allergy may also have undesirable consequences. Frequently, an elimination diet is absolutely necessary to prevent potentially life-threatening food allergic reactions. Allergen elimination can also ease chronic symptoms, such as atopic dermatitis, when a food is proven to trigger symptoms. However, removing a food with proven sensitivity to treat chronic symptoms may increase the risk of an acute reaction upon reintroduction or accidental ingestion after long-term avoidance, so it is not without risk. Additionally, it is not recommended to avoid foods in an attempt to control chronic symptoms such as AD and EoE when allergy to the specific food has not been demonstrated. Ultimately, allergen elimination goals are to prevent acute and chronic food allergic reactions in the least restrictive, but also the safest environment to supply a balanced diet that promotes health and growth and development in children.

In the past two decades, food allergy has emerged as an important public health issue in countries with a western life-style. Current management of food allergy relies on dietary avoidance and there is no therapy proven to restore permanent oral tolerance to food. This review focuses on novel approaches to allergen-specific therapy for IgE-mediated food allergy. Oral immunotherapy alone or in combination with anti-IgE antibody is likely to advance into clinical practice in the more immediate future. However, these approaches have to be further validated in large clinical trials before entering clinical practice. Diets containing extensively heated (baked) milk and egg for the majority of milk- and egg-allergic patients represent a safer alternative approach to food oral immunotherapy and are already changing the paradigm of strict dietary avoidance for majority of milk and egg-allergic children.

PURPOSE OF REVIEW/OBJECTIVE:To review current evidence on food oral immunotherapy (OIT). RECENT FINDINGS/RESULTS:Desensitized state, defined as the ingestion of a substantial amount of food in the home diet that protects from severe reactions to accidental exposures, can be achieved by approximately 50-75% of the children treated with OIT. The rate of permanent tolerance is unknown; the longer duration of OIT may result in permanent tolerance. Side effects are common both during the initial dose escalation and during home dosing. Most reactions are mild (oral pruritus, abdominal discomfort, and rashes) and decrease in frequency with the longer duration of OIT. Severe reactions treated with epinephrine have been reported during home dosing. Factors associated with increased risk of reactions to previously tolerated doses during home dosing include exercise, viral infection, dosing on empty stomach, menses, and asthma exacerbation. SUMMARY/CONCLUSIONS:These preliminary data on OIT are encouraging. Additional studies must answer multiple questions including optimal dose, ideal duration of oral/sublingual immunotherapy, degree of protection, efficacy for different ages, severity and type of food allergy responsive to treatment and need for patient protection during home administration. Until these questions are answered in rigorous multicenter randomized and placebo-controlled trials, OIT remains an experimental approach with not sufficiently well established risk-to-benefit ratio.

BACKGROUND:An inactivated influenza vaccine produced in canine kidney cells (MDCK 33016-PF) contains no egg proteins and may be used to immunize egg-allergic patients. Although no major dog allergens were identified in MDCK 33016-PF cells, minor dog allergens might be present and cause reactions in dog-allergic individuals. OBJECTIVE:To evaluate the allergenicity of the inactivated influenza vaccine produced in cell culture in a mediator release assay. METHODS:Rat basophil leukemia (RBL) cells transfected with human IgE receptor-1 were sensitized with sera from dog-allergic adults with positive skin prick test reactions to dog extract and detectable dog dander IgE and were stimulated with serial dilutions of vaccine and dog dander extract. N-hexosaminidase release (NHR) was used as a marker of RBL cell degranulation. Western blots were performed, and UniCAP was used to measure dog-specific IgE antibody levels. RESULTS:The median (interquartile range) level of dog dander IgE was 8.31 kU(A)/L (1.895-14.5 kU(A)/L) and of dog epithelium IgE was 3.19 kU(A)/L (0.835-6.27 kU(A)L). Median (range) maximum NHR (at the first 10-fold dilution) was 0% (0%-1.4%) to vaccine and 10.2% (0%-35.9%) to dog dander (P < .001). In an egg-allergic control subject, the maximum NHR to a vaccine cultured in chick embryo and containing egg protein was 10.2%. IgE antibodies in pooled sera did not bind to vaccine on immunoblots but produced strong binding to dog dander and epithelium extracts. Serum from an egg-allergic control subject strongly bound embryonated egg-derived vaccine. CONCLUSION/CONCLUSIONS:An influenza vaccine produced in continuous canine kidney cells did not trigger degranulation in RBL cells passively sensitized with human anti-dog IgE.

Egg allergy is one of the most frequent food allergies in children below the age of three. Common symptoms of egg allergy involve frequently the skin as well as the gut and in more severe cases result in anaphylaxis. Non-IgE-mediated symptoms such as in eosinophilic diseases of the gut or egg-induced enterocolitis might also be observed. Sensitization to egg white proteins can be found in young children in absence of clinical symptoms. The diagnosis of egg allergy is based on the history, IgE tests as well as standardized food challenges. Ovomucoid is the major allergen of egg, and recent advances in technology have improved the diagnosis and follow-up of patients with egg allergy by using single allergens or allergens with modified allergenic properties. Today, the management of egg allergy is strict avoidance. However, oral tolerance induction protocols, in particular with egg proteins with reduced allergenic properties, are promising tools for inducing an increased level of tolerance in specific patients.