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.

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.

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.

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.

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.

Subjective oral symptoms are insufficient predictors of a positive oral food challenge.

BACKGROUND: Subjective oral symptoms, especially if recurrent, might lead to termination of an oral food challenge (OFC) for fear of a subsequent severe reaction. METHODS: In a single-center retrospective cohort study, oral food challenges to milk, egg, peanut, sesame, or tree nuts performed between January 2016 and January 2018 in patients aged ≥3 years, at the Institute of Allergy, Immunology and Pediatric Pulmonology in Shamir Medical Center, were analyzed. Subjective oral symptoms during the challenge were documented, and their association with the challenge outcome was examined. RESULTS: A total of 323 patients underwent 652 oral food challenges to the investigated foods (milk, 71; egg, 22; peanut, 48; sesame, 24; and tree nuts, 487). Subjective oral symptoms were experienced in 237 (36.3%) of all OFCs performed, and their rate was comparable across most foods tested. The rate of positive challenges was significantly higher when subjective oral symptoms were experienced during the challenge than when they were not (69.6% vs 30.4%, respectively, P < .001). However, the false-positive rate of such symptoms in predicting a positive food challenge was 30.3% for all foods; peanut, 40%; sesame, 27.3%; milk, 35.5%; egg, 33%; and tree nuts, 28.4%. Overall, subjective oral symptoms (SOS) provided sensitivity of 56.7, specificity 80.4, PPV 69.6, and NPV 69.0 for predicting OFC outcome. Importantly, reactions during positive challenges with and without subjective oral symptoms were comparable to severity. CONCLUSIONS: Continuing OFCs with subjective oral symptoms is recommended for it will prevent false-positive results in a third of cases without increasing patients' risk.

Medical clown support is associated with better quality of life of children with food allergy starting oral immunotherapy.

BACKGROUND: The start of oral immunotherapy (OIT) for food allergy is a critical period in the treatment process, with a potential to influence patient quality of life (QOL) and subsequently treatment outcome. The association of medical clowning with QOL at OIT initiation was examined. METHODS: Children aged 4-12 years supported by a medical clown (MC) during the induction week of OIT for food allergy were studied. Children in the same age range starting OIT without the support of a MC served as controls. Parents of all children completed the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF), and children aged 8-12 years completed the Food Allergy Quality of Life Questionnaire-Child Form (FAQLQ-CF). QOL scores of parents and children with and without a MC support were compared. RESULTS: Children with (n = 88) and without (n = 212) the support of a MC were comparable in demographics and clinical characteristics. The study group had a significantly lower single highest tolerated dose compared to controls (57 ± 83 vs 162 ± 274 mg protein, respectively, P < .001). Parental perception of the QOL of children was not associated with a MC support (P = .81) but rather with previous reaction severity (P < .01). In contrast, the QOL of children aged 8-12 years (n = 119) was positively associated primarily with a MC support, total score 3.7 ± 1.1 vs 4.6 ± 1.3 (P < .001). CONCLUSIONS: While the perception of QOL of parents of children with food allergy at OIT initiation is mainly associated with previous reaction severity, the QOL of the children themselves is primarily positively associated with MC support.

Combinatorial advantage of Ses i 1-specific IgE and basophil activation for diagnosis of sesame food allergy.

BACKGROUND: The prevalence of sesame food allergy (SFA) is increasing worldwide with the potential of anaphylactic reactions upon exposure. Utility of specific component IgE testing as an alternative to the oral food challenge (OFC), the diagnostic standard, is being investigated. METHODS: Patients (n = 42) with suspected SFA completed an open OFC to sesame. Diagnostic testing included serum levels of Ses i 1-specific IgE, skin prick test with high-protein extract, and basophil reactivity (% induced CD63 expression) for each patient. The diagnostic utility of these tests was evaluated at a 95% sensitivity, with the outcome measure being the number of OFCs required. RESULTS: Twenty-seven patients (64%) were diagnosed with SFA. Ses i 1 IgE differed significantly between allergic and tolerant patients (p = .0001). ROC curve analysis for Ses i 1 IgE yielded an AUC of 0.88 ± 0.05. Levels of Ses i 1 IgE correlated to induced CD63+ expression on basophils (p = .0001). Ses i 1 IgE was not sufficiently robust as a single step for diagnosis. Used concurrently, BAT and Ses i 1 IgE yielded correct positive classifications for 25 of 27 sesame-allergic patients with two false positives (93% PPV). Both tests were negative in 5 non-allergic patients. Patients with divergent Ses i 1 IgE and BAT results required OFC (n = 10, 24% of patients). Alternatively, sequential use of BAT, ruling in SFA followed by Ses i 1 IgE diagnosing non-allergic patients, yielded a 89% PPV, with 19% requiring OFC. CONCLUSION: Ses i 1 IgE and BAT used together can decrease the need for OFC in most SFA patients. A prospective cohort trial is necessary to validate these results.

Home epinephrine-treated reactions in food allergy oral immunotherapy: Lessons from the coronavirus disease 2019 lockdown.

BACKGROUND: Oral immunotherapy (OIT) is effective in desensitizing patients with food allergy but adverse reactions limit its use. OBJECTIVE: To study the effect of the coronavirus disease 2019 lockdown in Israel between March 15, 2020, and April 30, 2020, on the incidence of home epinephrine-treated reactions. METHODS: All patients who were in the up-dosing phase of OIT for greater than or equal to 1 month during the lockdown, or a respective period in years 2015 to 2019, were studied. The incidence of home-epinephrine treated reactions during the 2020 lockdown was compared with that in the respective period in 2015 to 2019 and to periods before and after the lockdown. RESULTS: A total of 1163 OIT treatments were analyzed. Two epinephrine injections occurred during 2020 (0.7%) compared with 29 injections (3.28%) during 2015 to 2019 (P = .03). Patients treated in 2020 were older (8.1 vs 7 years, P < .01) and had a significantly lower single highest tolerated dose (12 vs 20 mg protein, P < .01). The rate of milk-OIT was lower (P = .01), but the total number of milk treatments was higher (99 vs 71 to 82) in 2020 compared with 2015 to 2019. On multivariate analysis, treatments during the 2020 lockdown were performed in older patients (P = .001), primarily for nonmilk (P = .03), began with a lower single highest tolerated dose (P = .006), and were associated with significantly less home epinephrine-treated reactions (P = .05) compared with those in 2015 to 2019. Patients treated in 2020 experienced more epinephrine-treated reactions in adjacent periods before (n = 8) and after (n = 6) the lockdown. CONCLUSION: The lower rate of home epinephrine-treated reactions during the coronavirus disease 2019 lockdown in Israel suggests that potentially avoidable triggers contribute significantly to the rate of adverse reactions during OIT.

Quality of life of children aged 8-12 years undergoing food allergy oral immunotherapy: Child and parent perspective.

BACKGROUND: Oral immunotherapy (OIT) for food allergy improves the quality of life (QOL) of children from parental perspective but little is known about the child perception. METHODS: The Food Allergy Quality of Life Questionnaire-Child Form (FAQLQ-CF) was administered to children aged 8-12 years, and the FAQLQ-Parent Form (FAQLQ-PF) was administered to their parents at the start of OIT for milk, egg, peanut, sesame, or tree nuts, at the end of up-dosing, and after 6 months of follow-up. Food-allergic children not undergoing OIT served as controls. Children QOL scores were compared to their parents. RESULTS: The total FAQLQ-CF score of 103 children undergoing OIT improved significantly from start of OIT (median (IQR); 4.8, 3.8-5.7) to end of up-dosing (3.9, 3-5.2) (P < .001). A greater improvement was noted in the 56 children who reached a follow-up visit, from 5.0 (3.7-5.8) at OIT start to 3.1 (1.8-5.0) on follow-up, (P < .001). In contrast, FAQLQ-CF scores of control patients improved mildly and nonsignificantly between the two time points from 5.3 (4.3-5.7) to 4.8 (3.6-6.0), (P = .13). The improvement in the total FAQLQ-CF scores from OIT start to follow-up was significantly greater compared to the change in control patients during observation (P = .015). Parents reported better QOL scores compared to their children at all stages of OIT (start 4.0, 3.2-5, P = .004; end of up-dosing 2.9, 1.9-4.7, P = .04; follow-up 2.2, 1.6-3.6, P = .003). CONCLUSIONS: QOL of food-allergic children undergoing OIT improves significantly compared to controls. Parents perceive QOL to be better than the perception of the children.