Faculty Bibliography

Baked milk (BM) and baked egg (BE) diets are increasingly used in the management of milk and egg allergy, rather than avoidance. Children with tolerance versus reactivity to BM and BE may have smaller skin prick test and lower specific IgE, and BM-tolerant children have less basophil reactivity and more peripheral T regulatory cells. However, most milk- and egg-allergic children tolerate BM and BE and an individual's reactivity is unpredictable. Non-reactivity is due to conformational changes in the allergens. Significant differences in the published advice about methods of introduction exist from graded introduction at home to a medically supervised full dose. These approaches carry different risks and may have different immunological effects. Reactivity to BM is a predictor of a severe milk allergy. Therefore, medical supervision for BM and BE introduction is prudent. The baked diet allows dietary liberation. Most, but not all, BM- and BE-tolerant children continue eating the baked foods. The prognosis of children who can eat BM and BE is favorable with likely resolution of their allergy over the next few years. Murine models of BE diets demonstrate that heated egg can impart clinical protection against anaphylaxis and cause immune changes. Most observational human studies of BM and BE diets demonstrate clinical resolution of allergy and favorable immune changes versus regular care controls. However, the one randomized controlled trial for the BE diet in BE-tolerant children did not support an immune-modifying effect of the BE diet. Another study of BE immunotherapy is expected to be completed in 2018. There is currently no evidence for prevention of allergy with the baked diets. There may be a future role for BM and BE in liberating the diets of individuals with non-IgE-mediated allergy given recent studies that a subset of these patients can consume BM without a clinical reaction.

With rising prevalence of food allergy (FA), allergen-specific immunotherapy (AIT) for FA has become an active area of research in recent years. In AIT, incrementally increasing doses of inciting allergen are given with the goal to increase tolerance, initially through desensitization, which relies on regular exposure to allergen. With prolonged therapy in some subjects, AIT may induce sustained unresponsiveness, in which tolerance is retained after a period of allergen avoidance. Methods of AIT currently under study in humans include oral, sublingual, epicutaneous, and subcutaneous delivery of modified allergenic protein, as well as via DNA-based vaccines encoding allergen with lysosomal-associated membrane protein I. The balance of safety and efficacy varies by type of AIT, as well as by targeted allergen. Age, degree of sensitization, and other comorbidities may affect this balance within an individual patient. More recently, AIT with modified proteins or combined with immunomodulatory therapies has shown promise in making AIT safer and/or more effective. Though methods of AIT are neither currently advised by experts (oral immunotherapy [OIT]) nor widely available, AIT is likely to become a part of recommended management of FA in the coming years. Here, we review and compare methods of AIT currently under study in humans to prepare the practitioner for an exciting new phase in the care of food allergic patients in which improved tolerance to inciting foods will be a real possibility.

Food protein-induced enterocolitis syndrome (FPIES) is a non IgE-mediated gastrointestinal food allergy that presents with delayed vomiting after ingestion primarily in infants. While the pathophysiology of FPIES is poorly understood, the clinical presentation of acute FPEIS reactions has been well characterized. The first International Consensus Guidelines for the Diagnosis and Management of Food Protein-induced Enterocolitis Syndrome were published in 2017 and reviewed epidemiology, clinical presentation, and prognosis of acute and chronic FPIES. The workgroup outlined clinical phenotypes, proposed diagnostic criteria, and made recommendations on management. This article summarizes the guidelines and adds recent updates. FPIES is gaining recognition, however there continues to be delays in diagnosis and misdiagnosis due to overlap of symptoms with over conditions, lack of a diagnostic test, and because some of the common trigger foods are not thought of as allergenic. More research into disease mechanisms and factors influencing differences between populations is needed.

Background/UNASSIGNED:Naturally occurring botulism is rare, but a large number of cases could result from unintentional or intentional contamination of a commercial food. Despeciated, equine-derived, heptavalent botulinum antitoxin (HBAT) is licensed in the United States. Timely treatment reduces morbidity and mortality, but concerns that botulinum antitoxin can induce anaphylaxis exist. We sought to quantify the allergy risk of botulinum antitoxin treatment and the usefulness of skin testing to assess this risk. Methods/UNASSIGNED:We conducted a systematic review of (1) allergic reactions to botulinum antitoxin and (2) the predictive value of skin testing (ST) before botulinum antitoxin administration. We searched 5 scientific literature databases, reviewed articles' references, and obtained data from the HBAT manufacturer and from the Centers for Disease Control and Prevention. Anaphylaxis incidence was determined for HBAT and previously employed botulinum antitoxins. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of ST for anaphylaxis related to HBAT and other botulinum antitoxins. Results/UNASSIGNED:Seven articles were included. Anaphylaxis incidence was 1.64% (5/305 patients) for HBAT and 1.16% (8/687 patients) for all other botulinum antitoxins (relative risk, 1.41 [95% confidence interval, .47-4.27]; P = .5). Observed values for both PPV and NPV for HBAT-ST (33 patients) were 100%. Observed PPVs and NPVs of ST for other botulinum antitoxins (302 patients) were 0-56% and 50%-100%, respectively. There were no reports of fatal anaphylaxis. Conclusions/UNASSIGNED:Considering the <2 % rate of anaphylaxis, fatal outcomes, modest predictive value of ST, resource requirements for ST, and the benefits of early treatment, data do not support delaying HBAT administration to perform ST in a mass botulinum toxin exposure. Anaphylactic reactions may occur among 1%-2% of botulinum antitoxin recipients and will require epinephrine and antihistamine treatment and, possibly, intensive care.

PURPOSE OF REVIEW/OBJECTIVE:We focus on recent advances regarding the epidemiology, physiopathology, diagnosis and managements of non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs), particularly food protein-induced enterocolitis syndrome (FPIES). RECENT FINDINGS/RESULTS:The first international FPIES diagnostic and management guidelines have been recently published. Although FPIES largely remains a diagnosis of exclusion, it may be more prevalent than previously thought. Ondansetron has emerged as a major tool for the treatment of FPIES acute reactions. Recent data also suggest an important role for innate immune cells in FPIES pathogenesis. SUMMARY/CONCLUSIONS:Despite major advances in the diagnosis and management of non-IgE-GI-FAs, particularly FPIES, the lack of specific diagnostic tests and biomarkers to guide clinical management remains challenging.