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.

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.

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.

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.

Long-term outcome of peanut oral immunotherapy-Real-life experience.

BACKGROUND: Oral immunotherapy (OIT) is currently recommended as a treatment option for peanut-allergic patients. Data regarding its long-term compliance and efficacy in real life are required. METHODS: Peanut-allergic patients aged ≥4 years were enrolled in a single-center clinical OIT program. Buildup to 3000 mg peanut protein was performed. Patients reaching this dose before or after 12/2014 were instructed to consume 3000 or 1200 mg daily, respectively. Patients were followed ≥6 months after reaching maintenance and rechallenged to 3000 mg. RESULTS: Of the 145 patients studied, 113 (77.9%) were fully desensitized to 3000 mg and 133 (91.7%) were desensitized to ≥300 mg. 21/145 patients (14.5%) required adrenaline for home-dose reactions during buildup. Non-anaphylactic gastrointestinal symptoms, experienced by 9 patients (6.2%), reversed with dose reduction. Of the 111 patients available for analysis 6 months after reaching 3000 mg, 97 (87.4%) continued regular peanut consumption. Only 2/111 patients (1.8%) required adrenaline over the long-term (median, range; 18, 6-75 months) follow-up. Adherence to treatment was significantly higher in patients consuming 1200 mg (73/76, 96.1%) vs those consuming 3000 mg (24/35, 72.2%), (P = .001). A higher maintenance dosage and home adrenaline requirement during buildup predicted adherence cessation (OR 12.5, P = .001; and OR 7.8, P = .02, respectively). 63/64 patients (98.4%) consuming 1200 mg maintenance dose were successfully rechallenged to 3000 mg. CONCLUSIONS: This real-life experience demonstrates the efficacy of peanut OIT long-term. A lower maintenance dose minimized treatment cessation while maintaining desensitization. OIT should be performed in qualified centers given the prevalence of adverse reactions, particularly during buildup.

Risk factors for reduced bone mineral density measurements in milk-allergic patients.

BACKGROUND: Earlier studies noted that young adults with IgE-mediated cow's milk allergy (IgE-CMA) have significantly lower bone mineral density (BMD) than age- and gender-matched controls. We sought to identify additional risk factors contributing to the low BMD in IgE-CMA patients. METHODS: Postpubertal (defined by Tanner stage V) IgE-CMA patients (n = 78; 16- to 30-year-old females and 17.5- to 30-year-old males) were evaluated prospectively for BMD using a DXA scan, serum values of bone turnover factor, and dietary and lifestyle questionnaires. Patients receiving > 2 short courses of systemic steroid treatments were excluded. RESULTS: Abnormal BMD measurements (T- or Z-scores < -1.0) of the lumbar vertebrae, femoral neck, or hip were noted in 60 patients, while normal BMD values were present in 18 patients, despite similarly decreased calcium intakes between the groups (P = 0.92). Patients with abnormal BMD were more likely to be asthmatic (P = 0.014), have a lower weight z-score (P = 0.007), have a decreased percent caloric intake derived from fat (P = 0.01), and have an increased carbohydrate intake (P = 0.03), in comparison with the normal-BMD group. Serum values of bone turnover were similar between the groups. On multivariate regression analysis, only asthma significantly (P = 0.006) increased the risk for osteopenia and osteoporosis (OR 38.5, 95% CI 2.8-500). Fitting continuous z-scores into a regression model, both asthma and weight z-score were significant (adjusted r2  = 0.272). Asthma was significantly overrepresented in osteopenic and osteoporotic subpopulations while decreased weight only in patients with osteoporosis. CONCLUSIONS: In the context of a low calcium intake, asthma and weight are independent risk factors for decreased BMD in IgE-CMA patients.

Food allergy to previously tolerated foods: Course and patient characteristics.

BACKGROUND: The acquisition of food allergy (FA) to previously safely consumed basic food proteins is an unusual presentation of immunoglobulin E (IgE)-mediated allergic disease. OBJECTIVE: We sought to characterize patients who developed FA to previously tolerated foods (FA-PTF), including underlying reasons for and length of elimination diet of previously tolerated foods. METHODS: Patients (n = 30) with complaints consistent with FA to foods previously consumed safely were evaluated. Clinical history was obtained, and skin prick testing and graded oral food challenges (OFC) were performed. One fatal case of FA-PTF was reported by a physician. RESULTS: Twenty-two of 30 patients (ages 1.2-50 years) were diagnosed with FA-PTF by OFC to milk (n = 17), egg (n = 2), and peanuts (n = 3). One additional patient with FA-PTF had a fatal reaction to milk. Anaphylactic reactions were reported in 12 of these 23 FA-PT patients (52%); 8 experienced multiple episodes. Atopic dermatitis was diagnosed in 52% (12/23) of patients, 8 of 12 as severe; overall, 18 of 23 (78%) of patients had marked personal atopic background. Sixteen patients (70%) initiated an elimination diet, 12 of whom did so on advice from a health care provider, before the appearance of allergic symptoms. However, in 4 patients with FA-PTF, reactivity to the food protein emerged during uninterrupted consumption. CONCLUSION: Food allergy to previously tolerated foods primarily appears after an elimination diet in atopic patients. Anaphylactic reactions are common. Health care providers should consider these risks before recommending elimination diet of tolerated foods.

Patient quality of life following induction of oral immunotherapy for food allergy.

BACKGROUND: Patient quality of life improves following successful completion of oral immunotherapy (OIT), but the process itself might have undesirable effects. We aimed to evaluate patient quality of life following OIT initial induction. METHODS: The Hebrew version of the Food Allergy Quality of Life Questionnaire-Parental Form (FAQLQ-PF) was validated and administered to the parents of children following the first week of OIT for food allergy (n = 119). Patient demographics and clinical history as well as the course of initial induction week were reviewed. RESULTS: Pre-OIT severity of food allergy, defined as severity of reactions due to accidental exposure to the allergenic food (anaphylactic reactions, p = 0.017; epinephrine use, p = 0.049; emergency room referrals p = 0.003; and hospital admissions, p = 0.015) and a lower number of tolerated doses during initial induction, reflective of a lower maximal tolerated dose for the different allergens (p = 0.011) were associated with worse total FAQLQ-PF scores. The number of tolerated doses during induction and pre-OIT emergency room referrals remained significantly associated with worse total score of the FAQLQ-PF on multivariate analysis (p = 0.016 and p = 0.005, respectively). The correlation between the number of tolerated doses and quality of life scores was moderate-strong primarily in children aged 6-12 years (Total score, r = -0.41, p = 0.001; Emotional Impact r = -0.42, p = 0.001; Food Anxiety, r = -0.38, p = 0.002; Social and Dietary Limitations, r = -0.33, p = 0.009). CONCLUSIONS: Pre-OIT reaction severity affects quality of life in both preschool and school-aged food-allergic children. In contrast, a lower maximal tolerated dose during OIT induction is associated with worse indices of quality of life primarily in children aged 6-12 years.

Efficacy of baked milk oral immunotherapy in baked milk-reactive allergic patients.

BACKGROUND: Patients with IgE-mediated cow's milk allergy who are nonreactive to baked milk (BM) can be desensitized with BM to promote tolerance to unheated milk (UM). OBJECTIVE: We sought to test whether patients who are BM reactive can progress in BM oral immunotherapy (OIT) and become desensitized to UM as well. METHODS: Fifteen patients (>4 years) who previously failed to complete our milk OIT program were enrolled into the BM OIT protocol. A dose of BM (180 °C for 30 minutes) which was less than the eliciting dose was increased 50% monthly while under medical supervision until the primary outcome dose of 1.3 g/d BM protein was achieved. Basophil reactivity and milk protein-specific IgE binding were analyzed at the first round of BM OIT therapy (T0) and at 12 months of BM treatment. RESULTS: In terms of the primary outcome, only 3 (21%) of 14 patients tolerated the 1.3 g/d BM dose. Although some patients initially progressed in BM OIT, 8 of 11 failed because of IgE-mediated reactions. Three did not complete the program because of non-IgE-mediated factors. An increase in challenge threshold to UM was noted in patients continuing until 12 months (P = .003), including those among whom reactions precluded continuation in the program. Patients (n = 3) who successfully reached maintenance had decreased milk-specific IgE reactivity. Furthermore, the mean difference at T0 between induced HM and UM percentages of CD203c expression was significantly lower in patients who successfully completed BM OIT than in those who did not (-11% vs 4.4%, P = .0002), which is consistent with their decreased clinical reactivity to BM. CONCLUSIONS: Although use of hypoallergenic BM in OIT is a promising therapy, care must be taken before its administration in BM-reactive patients because of the risk for anaphylaxis and only limited increase in challenge threshold attained.

[THE IMPORTANCE OF "MILK BONES" TO "WISDOM BONES" - COW MILK AND BONE HEALTH - LESSONS FROM MILK ALLERGY PATIENTS].

The necessity of milk consumption in the western diet is a subject of intense controversy. One of the main benefits of milk is that it is the main source of dietary calcium. Calcium is a major bone mineral, mandatory for bone health. Its supply is derived exclusively from external dietary sources. During the growth period, an increased calcium supply is needed for the process of bone mass accumulation. An optimal bone mass achieved by the end of the growth period may be protective later in life against the bone mass loss that commonly occurs. This in turn, can be preventative against the occurrence of osteoporosis and the development of spontaneous bone fractures. Over the past several decades, an increased incidence of osteoporosis has been documented in western countries, leading to high rates of morbidity and mortality in the middle-aged and geriatric population. Many studies have investigated the dietary calcium requirements for different ages, to achieve and maintain proper bone health. Based on their results, guidelines concerning calcium intake in every stage of life have been published by national and international organizations. In the western diet, it is difficult to achieve the recommended calcium intake without milk consumption. Moreover, calcium bioavailability for intestinal absorption is high. Several studies have recently raised doubts concerning the amounts of calcium intake in the western diet and its effectiveness in preventing osteoporosis. The main disadvantage of these studies is their being based on the patient's past memory recall of milk consumption. Patients with IgE-mediated cow's milk protein allergy are a unique population. Their lifetime negligible milk consumption is undisputed. A recent study investigated for the first time, the bone density of young adults with milk allergy at the end of their growth period. Their severe reduction in bone mineral density and dietary calcium intake defines them as a high risk group for the development of early osteoporosis. Another finding of this study was that normal bone density was found in milk allergic patients who started to consume milk after a successful desensitization program. Interestingly, these patients had consumed milk for a period of only 12-36 months and had only partially achieved the recommended dietary intake for calcium. It appears that dietary milk is essential for optimal peak bone mass. The required amounts of calcium and the preferred form for consumption, however, requires further investigation.

Oral immunotherapy in cow's milk allergic patients: course and long-term outcome according to asthma status.

BACKGROUND: Patients with asthma and food allergy comprise a high-risk group for life-threatening reactions at accidental exposure. OBJECTIVE: To examine the course and long-term outcome of patients with asthma completing milk oral immunotherapy. METHODS: Children at least 6 years old with (n = 101) and without (n = 93) asthma and IgE-mediated cow's milk allergy, undergoing milk oral immunotherapy from April 2010 to December 2011, were compared. Milk dose escalations were performed until patients reached full (>7.2 g of milk protein) or partial desensitization. Skin prick tests in all patients and spirometry in those with asthma were performed. Patients who completed treatment were followed for longer than 6 months. RESULTS: Before immunotherapy, patients with asthma, regardless of severity, had more anaphylactic reactions (84.2% vs 64.5%, P = .003), emergency department visits (68.3% vs 51.6%, P = .02), and hospital admissions (32.7% vs 18.3%, P = .03) compared with patients without asthma. Patients with asthma, regardless of severity, had more reactions and injectable epinephrine use during induction (P = .004) and home treatments (P = .007) of immunotherapy. Moderate to severe asthma was associated with a lower likelihood of reaching full desensitization (51.5% vs 68.8%, P = .019), but most patients with asthma (87 of 101, 86.1%), regardless of severity, reached a dose likely to protect them against accidental exposure. Most patients with asthma continued to consume milk protein freely after completion of immunotherapy. Although adverse reactions were still observed, severe reactions appeared to subside with time. CONCLUSION: Patients with asthma are at risk for more severe reactions and are less likely to reach full desensitization during food oral immunotherapy. However, most reach limited daily consumption and most who achieve full desensitization continue to consume milk protein freely after treatment.

A Web site-based reporting system for monitoring home treatment during oral immunotherapy for food allergy.

BACKGROUND: Reactions during the home treatment phase of oral immunotherapy (OIT) are not uncommon. An ongoing accurate reporting of home treatment outcomes is crucial for the safety and success of OIT. Previous reports have shown that as few as 20% of patients are truly compliant with paper-based diaries. OBJECTIVE: To develop a Web site-based electronic reporting system (web-RS) for monitoring home treatment during OIT for food allergy. METHODS: A web-RS was developed and incorporated a thorough questionnaire querying for pertinent data including the dose(s) consumed, occurrence and details of adverse reactions, treatment(s), and relevant potential exacerbating factors. All patients enrolled in milk, peanut, or egg OIT programs for at least 4 weeks from November 2012 through January 2014 were introduced to web-RS (n = 157). Successful reporting through web-RS was defined by consecutive reporting during the first home treatment phase (24 days) after its introduction. Comparisons were made with a previous group of OIT-treated patients (n = 100) who reported by E-mail. RESULTS: Successful reporting was achieved by 142 of 157 patients (90.44%) in contrast to a 75% success rate with E-mail (P = .0009). The odds for successful reporting using web-RS were 3.1 (95% confidence interval 1.6-6.3) times higher compared with using E-mail. Mild reactions were reported more frequently with web-RS (P = .0032). Patient reports were constantly available in real time for medical staff review. No complaints regarding web-RS feasibility were reported. One risk factor for failure to use web-RS was a patient's prior successful OIT experience without using web-RS (P = .012). CONCLUSION: A web-RS can be a powerful tool for improving OIT safety by achieving a high level of patient cooperation in reporting home treatment results.