Consumption of cow's milk formula in the nursery and the development of milk allergy.

BACKGROUND: The effect of the amount of transient cow's milk formula (CMF) consumed during the first days of life on IgE-cow's milk allergy (IgE-CMA) is unknown. METHODS: A cohort of 58 patients with IgE-CMA was identified from a large scale population-based study of 13,019 infants followed from birth. A group of 116 infants matched for sex and breastfeeding only duration (beyond the nursery period), and another random group of 259 healthy infants were used as controls. Parents were interviewed and the infants' medical records were searched to assess CMF consumption in the nursery. RESULTS: While 96% of the mothers of the 174 infants (58 with Cow's milk allergy and 116 controls) reported on exclusive breastfeeding during the stay in the nursery, CMF consumption was documented in 96 (55%) of the infants. Of those, most (57; 59%) received one to three feedings, 20 (21%) received four to nine feedings, and 19 (20%) received ≥10 feedings. Fewer formula feeds (1-3) were significantly more common in the allergic group than ≥4 feeds (p = 0.0003) and no feeds at all (p = 0.02) compared to controls (n = 116). Of those exclusively breastfed in the nursery, 13/23 allergic infants (57%) introduced CMF at age 105-194 days (the period with highest-risk for IgE-CMA) compared to 33/98 (34%) from the random control group (n = 259) (p = 0.04). CONCLUSIONS: Most infants end up receiving few CMF feeds in the nursery. Transient CMF in the nursery is associated with increased risk of IgE-CMA.

Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent.

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

Validation of the NUT CRACKER Diagnostic Algorithm and Prediction for Cashew and Pistachio Co-Allergy.

BACKGROUND: Because of the high cross-sensitization among tree nuts, the NUT CRACKER (Nut Co-reactivity-Acquiring Knowledge for Elimination Recommendations) study proposed a diagnostic algorithm to minimize the number of required oral food challenges (OFCs). OBJECTIVE: To validate the algorithm for cashew and pistachio allergy and determine markers for allergic severity. METHODS: Patients (n = 125) with a median age of 7.8 (interquartile range, 5.9-11.2) years with suspected tree nut allergy were evaluated prospectively with decision tree points on the basis of skin prick test (SPT), basophil activation test (BAT), and knowledge of the coincidence of allergies. Validation of allergic status was determined by OFC. Markers of clinical severity were evaluated using the combined original and prospective cohort (n = 187) in relationship to SPT, BAT, and Ana o 3-sIgE. RESULTS: Reactivity to cashew in SPT, BAT, and Ana o 3-sIgE and the incidence of abdominal pain on challenge were significantly higher in dual-allergic cashew/pistachio patients (n = 82) versus single cashew allergic patients (n = 18) (P = .001). All 3 diagnostic tests showed significant inverse correlation with log10 reaction doses for positive cashew OFC. The algorithm reduced overall the total number of OFCs by 72.0%, with a positive predictive value and negative predictive value of 93.0% and 99.0%, respectively. Cashew false-positives were observed primarily in hazelnut-allergic patients (P = .026). In this population, Ana o 3-specific IgE could diagnose cashew allergy with a sensitivity of more than 90% and a specificity of more than 95%. CONCLUSIONS: The NUT CRACKER diagnostic algorithm was validated and reduced the number of diagnostic OFCs required. Markers for severity phenotypes may guide oral immunotherapy protocols, improving the risk/benefit ratio for patients.

Comprehensive Diagnosis, Management, and Treatment of Sesame Allergy.

Sesame allergy prevalence varies regionally and by age, in the range of 0.1% to 0.9%. Reactions can be severe and potentially fatal. Resolution rates are in the range of 20% to 50%. The diagnosis requires a careful history and the use of tests, such as skin prick tests and serum sesame-specific IgE. The availability of serum IgE testing for the sesame protein Ses i 1 has improved diagnostic accuracy. The emerging potential for sesame basophil activation tests and additional new tests will likely improve diagnosis in coming years, further reducing the need for diagnostic oral food challenges. Although sesame proteins share homology with those in many foods, clinically relevant cross-reactivity appears uncommon. Nevertheless, sesame is a prominent allergen for those with multiple food allergies. Management may include strict avoidance, but sesame products vary dramatically in protein content. Many people with sesame allergy tolerate forms that are low in protein, such as scattered seeds, rather than sesame paste that is protein-dense. Thus, options in the approach to avoidance are possible. Studies suggest that sesame oral immunotherapy may be safe and effective, and this and additional treatment options are emerging. Here, we review the current comprehensive diagnosis, management, and treatment for sesame allergy.

Eosinophil-Associated Gastrointestinal Manifestations During OIT.

Gastrointestinal adverse events are common during oral immunotherapy (OIT) for food allergy and range from immediate IgE-mediated reactions to non-anaphylactic clinical presentations. This review aims to summarize recent findings on non-anaphylactic eosinophil-associated gastrointestinal adverse events during OIT. Two clinical presentations of non-anaphylactic eosinophil-associated gastrointestinal adverse events during OIT are identified, each with a different paradigm for treatment, and distinguished by their time of onset. In the first clinical entity, characterized by its onset early in the course of treatment, patients present with abdominal pain, nausea, and/or vomiting. The symptoms become evident typically within weeks to months of starting OIT. These symptoms, however, are not temporally related to the time of dose administration, as in the case of immediate IgE-mediated anaphylactic reactions. While esophageal biopsies, when performed, can demonstrate eosinophilic esophagitis (EoE), baseline esophageal eosinophilia has also been observed in food allergic patients prior to OIT. A potential non-invasive biomarker, the peripheral absolute eosinophil count (AEC), often rises during these reactions and subsides after dose reduction and subsequent resolution of symptoms. OIT can usually then be resumed, albeit at a slower pace, without a recurrence of symptoms. Risk factors for development of symptoms early during OIT include a high starting dose and a baseline AEC of greater than 600. The second, and much less frequently encountered, non-anaphylactic gastrointestinal adverse event related to OIT, presents months to years after initiating OIT. In this latter group, patients present with the classical clinical symptoms and endoscopic findings of EoE. In contrast to the acute onset group, peripheral eosinophilia is usually not observed in these cases. This OIT-associated EoE has shown good response to standard EoE treatment approaches of proton pump inhibitors or swallowed steroids. Most patients with eosinophil-associated adverse reactions are able to continue OIT and remain desensitized. Treatment approaches depend on the specific subtype of these reactions and relate to the stages of OIT treatment.

Proton pump inhibitors in eosinophilic esophagitis (EoE) related to oral immunotherapy: is it as effective as in other EoE?

Oral immunotherapy (OIT) may induce eosinophilic esophagitis (EoE). Proton pump inhibitors (PPIs) are an effective treatment for EoE. However, the effect of PPI treatment is not well established in patients with EoE induced by OIT. Our primary aim was to compare the clinical, endoscopic, and histological response rates to PPIs in children with EoE induced by OIT (EoE+OIT) versus EoE patients without OIT (EoE-OIT). The secondary aims are to describe the clinical and histological features of EoE+OIT. Demographic, clinical, endoscopic, and histological findings of patients with EoE in the gastroenterology clinic at Shamir Medical Center between March 2015 and December 2022 were collected. Comparisons were performed between EoE+OIT and EoE-OIT patients. The study included 42 children (74% male, mean age 11.2), of whom 31 had EoE-OIT and 11 had EoE+OIT. There were no significant differences between groups regarding sex, comorbidities, symptoms, or endoscopic and histological characteristics at diagnosis. All 42 children were treated with PPIs after diagnosis with or without diet changes. The rates of any clinical response were 83.9% and 90.1% in the EoE-OIT group and EoE+OIT group, respectively (p = 1.0). The rate of any endoscopic response was 74.2% for EoE-OIT and 81.8% for EoE+OIT (p = 0.54). Histologically, PPIs were even more effective in the EoE+OIT group, where only 18.2% had no histological response at all compared to 51.6% in the EoE-OIT group (p = 0.1). CONCLUSION: PPI treatment is as effective in EoE with OIT as it is in EoE due to other etiologies. WHAT IS KNOWN: • Proton pump inhibitor (PPI) treatment is effective for achieving clinical response and histologic remission in some patients with eosinophilic esophagitis (EoE). • EoE has also been reported to be triggered by oral immunotherapy (OIT). WHAT IS NEW: • PPI treatment in EoE with OIT is as effective as treatment for EoE due to other etiologies.

Sesame eliciting and safe doses in a large sesame allergic population.

BACKGROUND: Sesame is a significant food allergen causing severe and even fatal reactions. Given its increasing prevalence in western diet, sesame is listed as an allergenic food requiring labeling in the United States and EU. However, data on the population reaction doses to sesame are limited. METHODS: All sesame oral food challenges (OFCs), performed either for diagnosis or for threshold identification before the beginning of sesame oral immunotherapy (OIT) between November 2011 and July 2021 in Shamir medical center were analyzed for reaction threshold distribution. Safe-dose challenges with 90-120 min intervals were also analyzed. RESULTS: Two hundred and fifty patients underwent 338 positive OFCs, and additional 158 safe-dose OFCs were performed. The discrete and cumulative protein amounts estimated to elicit an objective reaction in 1% (ED01) of the entire cohort (n = 250) were 0.8 mg (range 0.3-6.3) and 0.7 mg (range 0.1-7.1), respectively, and those for 5% of the population (ED05) were 3.4 mg (range 1.2-20.6) and 4.5 mg (range 1.2-28.8), respectively. Safe-dose OFCs showed similar values of ED01 (0.8, 0.4-7.5 mg) and ED05 (3.4, 1.2-22.9 mg). While doses of ≤1 mg sesame protein elicited oral pruritus in 11.6% of the patients, no objective reaction was documented to this amount in any of the challenges, including safe-dose OFCs. CONCLUSIONS: This study provides data on sesame reaction threshold distribution in the largest population of allergic patients studied, with no right or left censored data, and with validation using a safe-dose OFC. It further supports the current methods for ED determination as appropriate for establishing safety precautions for the food industry.

Recipient-independent, high-accuracy FMT-response prediction and optimization in mice and humans.

BACKGROUND: Some microbiota compositions are associated with negative outcomes, including among others, obesity, allergies, and the failure to respond to treatment. Microbiota manipulation or supplementation can restore a community associated with a healthy condition. Such interventions are typically probiotics or fecal microbiota transplantation (FMT). FMT donor selection is currently based on donor phenotype, rather than the anticipated microbiota composition in the recipient and associated health benefits. However, the donor and post-transplant recipient conditions differ drastically. We here propose an algorithm to identify ideal donors and predict the expected outcome of FMT based on donor microbiome alone. We also demonstrate how to optimize FMT for different required outcomes. RESULTS: We show, using multiple microbiome properties, that donor and post-transplant recipient microbiota differ widely and propose a tool to predict the recipient post-transplant condition (engraftment success and clinical outcome), using only the donors' microbiome and, when available, demographics for transplantations from humans to either mice or other humans (with or without antibiotic pre-treatment). We validated the predictor using a de novo FMT experiment highlighting the possibility of choosing transplants that optimize an array of required goals. We then extend the method to characterize a best-planned transplant (bacterial cocktail) by combining the predictor and a generative genetic algorithm (GA). We further show that a limited number of taxa is enough for an FMT to produce a desired microbiome or phenotype. CONCLUSIONS: Off-the-shelf FMT requires recipient-independent optimized FMT selection. Such a transplant can be from an optimal donor or from a cultured set of microbes. We have here shown the feasibility of both types of manipulations in mouse and human recipients. Video Abstract.

Severe Anaphylactic Reactions to Home Doses of Oral Immunotherapy for Food Allergy.

BACKGROUND: Severe anaphylactic reactions to home doses may occur during food allergy oral immunotherapy (OIT). OBJECTIVE: To study the rate and risk factors for such reactions. METHODS: We studied all patients aged greater than 3.5 years who completed OIT in a single center between April 2010 and January 2020. All home epinephrine-treated reactions (HETRs) were identified. High-grade HETRs (HG-HETRs) were defined as HETRs involving respiratory (SpO2 of 94% or less), cardiovascular (low blood pressure), or central nervous system impairment (loss of consciousness). We investigated the rate and risk factors for HG-HETRs. RESULTS: A total of 1,637 OIT treatments were studied: milk (880), peanut (346), tree nuts (221), sesame (115), and egg (75). Of 390 identified HETRs, 30 HG-HETRs occurred during 27 treatments (1.65% of all treatments). Nearly all (26 of 30) were during milk OIT in patients with house dust mite (HDM) sensitization and asthma (26 of 30 each). Of the 30 patients with HG-HETRs, 21 recovered with one or two epinephrine treatments, but nine (0.55% of all treatments) did not respond to a second dose of epinephrine and were deemed to have refractory anaphylaxis. Three patients required intensive care unit admission and three received epinephrine drip, but none required ventilatory support. Risk factors for HG-HETRs included milk OIT (P = .031), asthma (P = .02) and HDM sensitization (P = .02). No specific triggers for HG-HETR were identified. Of patients with HG-HETRs, 25.9% were fully desensitized, including the four non-milk treated patients; 22.2% were partially desensitized; and 51.9% failed. CONCLUSIONS: High-grade HETRs are uncommon, particularly refractory anaphylactic reactions to home OIT doses. Although milk OIT, asthma, and HDM sensitization are the main risk factors for such reactions, identification of patients who are at risk is challenging.

Characteristics of patients diagnosed as non-allergic following food allergy oral immunotherapy referral.

BACKGROUND: Ascribing food allergy diagnosis to patients who are not allergic is well described, but its implications on oral immunotherapy (OIT) have not been studied. The aim was to study non-allergic patients referred for OIT. METHODS: All patients who began OIT at Shamir Medical Center between November 2015 and August 2020 were included. Medical records were reviewed, and skin prick tests (SPT) and/or specific IgE were measured. Patients were challenged to the index food. Allergic and non-allergic patients were compared. RESULTS: A total of 1073 patients were studied (milk, n = 327; egg, n = 41; peanut, n = 272; sesame, n = 130; and tree nuts, n = 303) and 87 (8.1%) were found non-allergic (milk, n = 21; egg, n = 6; sesame, n = 5; peanut, n = 29; tree nuts, n = 26). Predictors of being not allergic were no previous reaction to the index food (OR = 3.3, p = 0.001), not having asthma (OR = 2.4, p = 0.001), or HDM sensitization (OR = 2.0, p = 0.007), male sex (OR = 2.3, p = 0.004), and a smaller SPT wheal size (OR = 1.5, p < 0.001). CONCLUSIONS: A substantial number of patients referred for OIT are mislabeled with food allergy, suffer from unjustly food limitations and impairments in quality of life, and "take up" OIT places of true allergic patients. Awareness of OIT centers to this phenomenon is important. IMPACT: A significant number (8.1%) of patients referred for OIT are found not allergic to the food they intended to treat. This study characterizes non-allergic patients referred for OIT (a lack of previous reaction to the index food, a smaller or negative SPT wheal size, and less atopic co-morbidities) and discusses the implications of such referrals. Increased awareness by OIT centers to potential non-allergic patients referred for OIT is required, including screening of patients before treatment initiation, to minimize unnecessary treatments of non-allergic patients.

Efficacy and safety of food allergy oral immunotherapy in adults.

BACKGROUND: Oral immunotherapy (OIT) is an emerging method for treating food allergy in children. However, data regarding adults undergoing this process are lacking. METHODS: We retrospectively analyzed the medical records of patients with food allergy aged ≥17 years who completed OIT treatment between April 2010 and December 2020 at Shamir Medical Center. Data were compared with that of children aged 4 to <11 years and adolescents aged ≥11 to 17 treated during the same time period. RESULTS: A total of 96 adults at a median age of 22.3 years who underwent OIT for milk (n = 53), peanut (n = 18), sesame (n = 7), egg (n = 5), and tree nuts (n = 13) were analyzed and compared with 1299 children and 309 adolescents. Adults experienced more adverse reactions requiring injectable epinephrine, both during in-clinic up-dosing (49% vs. 15.9% and 26.5% for children and adolescents, respectively, p < 0.0001) and during home treatment (22.9% vs. 12.4%, p = 0.007 for children, and 17.5%, p = 0.23 for adolescents). Most adults (61.5%) were fully desensitized, but the rates of full desensitization were significantly lower than children (73.4%, p = 0.013). Significantly more adults (28.3%) undergoing milk OIT failed treatment than children (14.3%, p = 0.015) and adolescents (14.1%, p = 0.022), while failure rates in adults undergoing OIT for other foods were low (9.3%) and comparable with children and adolescents. CONCLUSIONS: OIT is successful in desensitizing most adults with IgE-mediated food allergy. Adults undergoing milk OIT are at increased risk for severe reactions and for OIT failure while failure rates in adults undergoing OIT for other foods are low.

Informing Risk Management for Patients With Cow's Milk Allergy Based on Threshold Dose Distributions Using Low-Dose Food Challenges.

BACKGROUND: The safe consumption of foods depends on their allergen content in relation to patients' lowest observed adverse effect level (LOAEL) and no observed adverse effect level (NOAEL), as well as other factors. In the case of milk, data on LOAEL and NOAEL are limited and conflicting. OBJECTIVE: To determine the threshold dose distribution and the lowest individual eliciting dose (ED) for milk in a large group of milk-allergic patients METHODS: Individuals with confirmed cow's milk allergy who underwent a diagnostic or pre-oral immunotherapy open milk oral food challenge at the Institute of Allergy, Immunology, and Pediatric Pulmonology at Shamir Medical Center between 2010 and 2015 were included. A subgroup of patients with severe milk allergy underwent a modified challenge with a 90- to 120-minute interval after a starting dose of 0.3 mg cow's milk protein. RESULTS: A total of 866 participants (193 with diagnostic challenges and 673 with pre-oral immunotherapy challenges) were included in the study. The discrete ED01 and ED05, or values derived in which 1% or 5% of the respective allergic population would be predicted to experience an allergic reaction, were 1.1 to 1.9 and 4.7 to 5.6 mg milk protein, respectively, and values for cumulative doses for ED01 and ED05 were 0.9 to 1.8 and 5.2 to 6.2 mg milk protein, respectively. No patients, including the most severely milk-allergic individuals who underwent the modified challenge, reacted to the first 0.3 mg protein dose. CONCLUSION: This report provides valuable information about milk NOAELs, LOAELs, and EDs that might assist regulators in decisions about food labeling in general, and milk in particular.

Factors associated with home epinephrine-treated reactions during peanut and tree-nut oral immunotherapy.

BACKGROUND: Home reactions requiring epinephrine administration, a marker of their severity, restrict the widespread use of oral immunotherapy (OIT), but their risk factors are largely not known. OBJECTIVE: To identify risk factors for such reactions during OIT to most allergenic foods. METHODS: All patients who began OIT for peanut, tree nuts, sesame, or egg allergy at the Shamir Medical Center between April 2010 and January 2020 were enrolled. The patients were instructed to use their epinephrine autoinjectors during reactions consisting of severe abdominal pain, significant shortness of breath, or lethargy, or whenever in uncertainty of reaction severity. Patients with and without home epinephrine-treated reactions (HETRs) were compared. RESULTS: A total of 757 OIT treatments for peanut (n = 346), tree nuts (n = 221; walnut n = 147, cashew n = 57, hazelnut n = 16, almond n = 1), sesame (n = 115), and egg (n = 75) allergies were administered to 644 patients. Eighty-three (10.9%) patients experienced HETRs. The highest rate of HETRs was experienced during walnut (20.4%) or hazelnut (25%) OIT, followed by peanut (9.8%), sesame (6.1%), egg (6.7%), and cashew (5.3%) OIT. Risk factors for HETRs included a reaction treated in an emergency department (ER) (P = .005) before starting OIT and a reaction treated with epinephrine during in-clinic induction (P < .001). Significantly fewer patients with (73.6%) than without (88.3%) HETRs achieved full desensitization (P = .001), but only a few patients with HETRs (8.4%) failed treatment. CONCLUSION: Previous reaction severity is the main predictor for HETRs during OIT. These reactions are more frequent during walnut and hazelnut OIT than during OIT for other foods studied. Most patients experiencing HETRs achieved desensitization.

Triggers for Home Epinephrine-Treated Reactions During Oral Immunotherapy for Food Allergy.

BACKGROUND: Home reactions requiring epinephrine treatment represent a significant obstacle to oral immunotherapy (OIT) and impair treatment outcome. OBJECTIVE: To identify potential triggers for such reactions for improvement of patient safety. METHODS: All patients aged older than 3.7 years who began an open-label OIT treatment program to milk, peanut, egg, sesame, or tree nuts in the Institute of Allergy, Immunology, and Pediatric Pulmonology at Shamir Medical Center between April 2010 and March 2018 were enrolled. Information on home epinephrine-treated reactions (HETRs) during the up-dosing phase of OIT was collected from the documentation in patients' files and the reports were transmitted by email and via a web reporting system. RESULTS: A total 1,270 OIT treatments were included (milk 780; peanut 256; egg 63; sesame 72; and tree nuts 99). Home epinephrine was administered in 200 treatments (15.7%) and in 70 of them a second epinephrine-treated reaction occurred. The leading identified triggers for HETRs were physical exercise temporally associated with administration of home dose (20%), and dose consumption during infectious disease (16.7%), or when fatigued (13.8%). The rate of first HETRs was highest (10.1%) to doses of 500 mg protein or less and particularly to 300 mg or less. The occurrence of first HETRs was highest (35.5%) during the first and decreased to 13.8% by the last of the 4-week home-treatment phase. Second HETRs occurred in a similar rate throughout these 4 weeks. The incidence of HETRs was highest during pollen season and vacation months. CONCLUSIONS: The identification of factors, some protocol-dependent, that trigger HETRs should assist in improving OIT safety.

Cashew oral immunotherapy for desensitizing cashew-pistachio allergy (NUT CRACKER study).

BACKGROUND: Oral immunotherapy (OIT) is a treatment option for patients with milk, egg, and peanut allergy, but data on the efficacy and safety of cashew OIT are limited. METHODS: A cohort of 50 cashew-allergic patients aged ≥4 years, who were consecutively enrolled into cashew OIT (target dose 4000 mg protein) between 4/2016 and 12/2019. Fifteen cashew-allergic patients who continued cashew elimination served as observational controls. Co-allergy to pistachio and walnut was determined. Full desensitization rate and associated immunological changes in both groups were compared. Patients fully desensitized to cashew were instructed to consume a dose of 1200 mg cashew protein for 6 months and were then challenged to a full dose. Patients with co-allergy to pistachio or walnut were challenged to the respective nut. RESULTS: Forty-four of 50 OIT-treated patients (88%) compared to 0% in controls tolerated a dose of 4000 mg cashew protein at the end of the study (odds ratio 8.3, 95% CI 3.9-17.7, p < 0.001). An additional three patients were desensitized to 1200 mg cashew protein, and three patients stopped treatment. Three patients (6%) were treated with injectable epinephrine for home reactions. Desensitized patients had decreased SPT, sIgE, basophil reactivity, and increased sIgG4, following treatment. Following cashew desensitization, all pistachio (n = 35) and four of eight walnut co-allergic patients were cross-desensitized to the respective nut. All (n = 44) patients consuming a low cashew dose for ≥6 months following desensitization passed a full-dose cashew OFC. CONCLUSIONS: Cashew OIT desensitizes most cashew-allergic patients and cross-desensitizes to pistachio. Safety is similar to OIT for other foods.

Advances, Practical Implementation, and Unmet Needs Regarding Oral Immunotherapy for Food Allergy.

Treatment of food allergy is a rapidly changing landscape, with arguably, the most significant advancement in recent years, the transition of oral immunotherapy (OIT) to clinical practice. As an innovation, OIT is a phase of rapidly increasing demand, particularly for some allergens such as peanut, egg, and milk, which have substantial evidence of efficacy. However, significant questions remain about how to best treat multiple food allergies and less common food allergies and how to optimize long-term safety and efficacy. This review summarizes the currently available resources for integrating food allergy OIT into clinical practice and focuses on the multiple remaining unmet needs such as providing an approach for OIT to food allergens for which there is no or limited evidence; practical issues related to food allergy treatment particularly when it is not going well; long-term outcomes and follow-up after OIT; and strategies to help meet the impending increase in demand.