Three-year prognosis after low-dose oral food challenge for children with wheat allergy.

BACKGROUND: Low-dose oral food challenge (LD-OFC) is an approach to avoid complete elimination in high-risk patients with wheat allergy (WA). We examined the 3-year prognosis after LD-OFC among patients who passed and failed LD-OFC. METHODS: Children with immediate-type WA aged ≤6 years with a history of reaction to ≤390 mg of wheat protein underwent their first LD-OFC with 52 mg (baseline LD-OFC). After passing the LD-OFC, children stepped up to 390, 1300, and 5200 mg step-by-step every 3-6 months. After failing LD-OFC, children repeated LD-OFC every 6-12 months. We assessed wheat tolerance defined as consuming 5200 mg without symptoms for 3 years after baseline LD-OFC. RESULTS: The median age of 124 children was 2.4 years, and the wheat- and ω-5-gliadin-specific immunoglobulin E (IgE) levels (kUA/L) were 23.6 and 2.1, respectively. Upon baseline LD-OFC, 57% passed (LD-tolerant), whereas 43% failed (LD-reactive). Within 3 years, 38% of the LD-reactive group passed re-administered LD-OFC, and 70% of all participants avoided complete elimination. The percentage of the participants who became capable of consuming 390 mg (87% vs. 18%), 1300 mg (78% vs. 13%), and acquired tolerance (70% vs. 13%) was significantly higher in the LD-tolerant group than in the LD-reactive group (p < 0.001). Predictors of persistent WA in the LD-tolerant group were older age (adjusted odds ratio, 1.63), ω-5-gliadin-specific IgE level (1.62 per 10-fold increase), and other food allergies (1.94). CONCLUSIONS: LD-tolerant patients frequently acquired wheat tolerance within 3 years. Even if once positive, one-third could pass the re-administered LD-OFC within 3 years.

Relationship between serum allergen-specific immunoglobulin E and threshold dose in an oral food challenge.

BACKGROUND: Several studies have reported threshold doses for food allergens. However, evidence regarding potential risk factors for low threshold doses is limited. Moreover, the relationship between threshold dose and specific immunoglobulin E (sIgE) levels to causative foods remains unclear. This study examined the relationship and the risk factors for a low threshold dose. METHODS: We recruited children with food allergies and examined the risk factors for a positive oral food challenge (OFC) with a low threshold dose and anaphylaxis. RESULTS: We evaluated 2501 children with food allergies (1667 [67%] boys; median age, 4.9 years) to eggs (n = 1096), milk (n = 671), wheat (n = 370), peanuts (n = 258), walnuts (n = 65), and cashews (n = 41). Of these patients, 234 (9%) reacted to ≤30 mg protein of causative foods and 620 (25%) reacted to ≤100 mg protein of causative foods. The sIgE level to causative foods was a significant independent factor for positive OFCs with a threshold dose of ≤30 mg for milk, wheat, and peanuts; ≤ 100 mg for eggs, milk, wheat, peanuts, and cashews; and anaphylaxis from eggs, milk, wheat, peanuts, and walnuts. High sIgE levels to causative foods were associated with a lower threshold dose of the OFC and anaphylaxis during the OFC. CONCLUSIONS: Approximately 9% of patients reacted to ≤30 mg protein of causative foods. The potential risks of anaphylaxis should be considered during OFCs for patients with elevated sIgE levels.

Natural History of Allergy to Hen's Egg: A Prospective Study in Children Aged 6 to 12 Years.

INTRODUCTION: There are limited reports on the natural history of hen's egg (HE) allergy (HEA) in children <6 years. We aimed to investigate the natural history of HEA in children aged 6-12 years and the factors affecting its tolerance acquisition. METHODS: Using the database in our hospital, a total of 137 patients diagnosed with a definitive immediate-type reaction to HE when they turned 6 years were enrolled, and the natural course of HEA was prospectively examined until patients turned 12 years. Tolerance was defined as being able to pass an oral food challenge to consume a half or whole heated HE or consume heated HE freely without symptoms. Thirty patients (21.9%) who were enrolled for oral immunotherapy and 21 (15.3%) who discontinued follow-up were considered dropouts. Kaplan-Meier estimation was used to evaluate the rate of tolerance. RESULTS: Fifty-five of the 137 patients (40.1%) had a previous HE anaphylaxis history; 61 (44.5%) patients had acquired tolerance to HE by age 12 years; and 25 (18.2%) continued total or partial HE elimination. The estimated acquired tolerance rates by ages 7, 9, and 12 years were 14.6%, 40.8%, and 60.5%, respectively. A previous history of HE anaphylaxis before 6 years of age, reacting to small amounts of heated HE by 6 years of age, and higher ovomucoid-specific immunoglobulin E values at the same age were associated with persistent HEA. CONCLUSION: This study provides important insights into the natural course of HEA beyond early childhood, with the acquisition of HE tolerance continuing throughout the duration of the study.

Phenotyping of immediate-type food allergies based on 10 years of research: A latent class analysis.

BACKGROUND: Food allergy is a disease with a diverse and variable natural history, and some patients may react to two or more food antigens. This study aimed to classify and characterize the long-term prognosis of infantile-onset, immediate-type food allergies, focusing on three major antigens in Japan: egg, milk, and wheat. METHODS: All children who visited our hospital with food allergies, including suspected cases, were prospectively registered in our medical database. Among the children in this database, subjects registered by the age of 1 year with immediate-type symptoms or sensitization to the above three antigens were included. The course of the subjects up to the age of 6 years was analyzed. Cox regression analysis and repeated-measures latent class analysis (LCA) were performed to reveal risk factors and tolerance patterns for food allergies. RESULTS: We included 915 patients with immediate-type food allergy symptoms and 276 sensitized asymptomatic patients in this study. The number of patients with immediate-type symptoms to egg, milk, and wheat was 609, 443, and 235, respectively. The number of patients with multiple food allergies was 302. The proportion of patients with tolerance to egg, milk, and wheat at 6 years of age was 74%, 69%, and 75%, respectively. LCA revealed 7 classes of prognosis for food allergies. The largest class was transient egg allergy alone (19.6%), and there were severe cases of multiple food allergies (6.5%). CONCLUSIONS: This study demonstrated the prognosis of food allergy classes in Japan, including multiple food allergies, with 7 classes with its own characteristics.

Risk factors for failing a repeat oral food challenge in preschool children with hen's egg allergy.

BACKGROUND: Children with hen's egg (HE) allergy and a positive initial oral food challenge (OFC) require rechallenge to assess for tolerance. However, the risk factors for a positive repeat OFC remain unclear. METHODS: We retrospectively analyzed data from 243 preschool children who failed an initial OFC with half a heated HE and repeated the same OFC after 6-24 months. Logistic regression models were used to determine risk factors for a positive repeat OFC, including factors that were ascertainable immediately after the initial OFC and at the repeat OFC as variables. RESULTS: The median age, egg white-, and ovomucoid-specific IgE (sIgE) were 3.5 years, 12.7, and 7.2 kUA /L, respectively. The median interval between OFCs was 12.4 months and repeat OFCs were positive in 132 (54%) patients. One multivariate analysis model indicated that risk factors for a positive repeat OFC included cumulative dose (adjusted odds ratio [aOR]:0.58), anaphylaxis (aOR: 3.09), total serum IgE (aOR: 0.41), ovomucoid-sIgE (aOR: 3.21), and age (aOR: 1.68) at the initial OFC. Another model indicated that the risk factors were cumulative dose (aOR: 0.59) and anaphylaxis (aOR: 3.41) at initial OFC and total serum IgE (aOR: 0.36), ovomucoid-sIgE (aOR: 4.93), and age (aOR: 1.30) at repeat OFC. CONCLUSION: Low threshold dose and severe symptoms at initial OFC, and low total serum IgE, high ovomucoid-sIgE and higher age at initial and repeat OFCs are risk factors for the persistence of HE allergy and they may be useful when deciding the rechallenge interval for heated HE in preschool children.

A randomized trial of oral immunotherapy for pediatric cow's milk-induced anaphylaxis: Heated vs unheated milk.

BACKGROUND: Severe reactions may develop during cow's milk (CM) oral immunotherapy (OIT). We investigated the safety and efficacy of low-dose OIT with heated milk (HM) or unheated milk (UM) in children with anaphylaxis. METHODS: Children with symptom onset after ingestion of 3-mL HM on a double-blind, placebo-controlled food challenge were randomly assigned to the HM (n = 17) or UM (n = 16) group. HM group ingested milk powder heated at 125°C for 30 seconds, whereas the UM group used UM. Patients were hospitalized for 5 days; the HM or UM was gradually increased to 3 mL/day; 3-mL/day ingestion was continued at home. One year later, the patients underwent 2-day consecutive 3- and 25-mL HM-oral food challenges (OFCs) after 2-week avoidance. RESULTS: At baseline, milk- and casein-specific immunoglobulin E (IgE) levels were 56.0 and 51.4 kUA/L in the HM group, and 55.2 and 65.6 kUA/L in the UM group, respectively. One year later, 35% and 18% in the HM group and 50% and 31% in UM group passed the 3 and 25 mL OFCs, respectively. Rates of moderate or severe symptoms and respiratory symptoms per home dose were significantly lower in the HM than in the UM group (0.7% and 1.2% vs 1.4% and 2.6%, respectively, P < .001). ß-lactoglobulin-specific IgG4 levels significantly increased from baseline only in the UM group, whereas casein-specific IgG4 levels significantly increased from baseline in both groups. CONCLUSIONS: HM-OIT induced immunological changes more safely than the UM-OIT. The possibility of lower treatment efficacy with HM-OIT needs to be evaluated in larger studies.

Safe egg yolk consumption after a negative result for low-dose egg oral food challenge.

BACKGROUND: Hen's egg is one of the most common allergens causing infantile food allergy. Consuming heated egg yolk slightly contaminated with egg white (EY with scEW) improves diet quality. Most children with egg allergies can safely consume 1/25 of a heated whole egg (low-dose egg). Although low-dose egg has similar antigenicity to EY with scEW, clinical reproducibility is unknown. We aimed to examine the safety of EY with scEW consumption after a negative result of low-dose egg oral food challenge (OFC). METHODS: In this prospective study, children aged <18 years with a history of immediate reaction to eggs were enrolled. We advised children and guardians to consume EY with scEW after a negative result of low-dose egg OFC and to record symptoms, if any. RESULTS: We evaluated 276 children with negative results for low-dose egg OFC who had previously shown reactivity to eggs. Their median age was 1.2 years. Boys accounted for 188 (68%) of the children. The median egg white-specific immunoglobulin E level was 11.7 kUA /L. At home, six children experienced mild symptoms. Skin symptoms were the most common. Among the six children, five were confirmed to continue the consumption of EY with scEW and one developed mild respiratory symptoms and continued to avoid eating eggs. CONCLUSION: Although a few children with egg allergies experience mild symptoms, most of them can ultimately consume EY with scEW. Consumption of EY with scEW after low-dose egg OFC seems safe and may improve their quality of life by making egg yolk products available.

Long-term follow-up of fixed low-dose oral immunotherapy for children with severe cow's milk allergy.

BACKGROUND: The efficacy and safety of cow's milk (CM) low-dose oral immunotherapy (LOIT) at one-year follow-up have been previously reported. We investigated the outcome of fixed long-term LOIT in children with severe CM allergy. METHODS: Children with positive reactions to oral food challenge (OFC) with 3 mL CM were included. The LOIT group (n = 33) ingested up to 3 mL CM for 1 year. After a two-week CM avoidance, 3 and 25 mL OFCs were performed. Children with positive reactions continued with 3 mL ingestion, with OFCs repeated yearly. Regular home consumption of 25 mL CM after passing the OFCs was defined as 25 mL short-term unresponsiveness (25 mL STU). The historical control group (n = 16) with reactions to 3 mL OFC eliminated daily CM ingestion. RESULTS: The proportion of 25 mL STU in the LOIT group was 27%, 52%, and 61% after 1, 2, and 3 years, respectively, and the 3-year percentage was significantly higher than that in the historical control group (13%, P = .002). In the LOIT group, only one child developed severe symptoms. Furthermore, in this group, CM- and casein-specific immunoglobulin E (sIgE) levels decreased significantly and casein-specific IgG and IgG4 levels increased significantly after 3 years, whereas the historical control group presented no significant change in these parameters. Baseline sIgE levels were significantly low in children achieving 25 mL STU. CONCLUSION: Continued fixed LOIT yields immunologic improvement and may be effective and safe for severe CM allergy.

[THE STATUS OF ADMISSION TO FACILITIES FOR CHILDREN WITH FOOD ALLERGIES].

BACKGROUND: To clarify the status of admission to facilities for food allergy (FA) children. METHODS: Guardians of FA children who underwent oral food challenges at Sagamihara National Hospital from September to December 2018 were enrolled. We surveyed the experience of refusal to enter facilities, the reason for refusal and so on using a self-administered questionnaire. RESULTS: We distributed a questionnaire to 205 guardians, of which 168 responded (response rate 82%). The median age (range) at the time of the survey was 4.5 (0 to 12) years old, 2 (1 to 11) food items had been removed at the time of admission, and 56 (33%) had a history of anaphylaxis before admission. Twenty-nine patients (17%) were prescribed an adrenaline auto injector. Twenty patients (12%) had been denied entry, the median number of refusals (range) was 1.5 (1 to 30). History of anaphylaxis before admission (odds ratio 2.80 [1.08-7.22]) and having 5 or more causative foods (odds ratio 3.44 [1.27-9.32]) were associated with admission refusal. 〔' Factors related to children with FA〕, 〔Factors related to facilities〕, and 〔Factors related to facility staff〕 were extracted as the reasons for refusal. CONCLUSIONS: In addition to the factors related to children with FA, the factors related to facilities and facility staff were related to admission refusal. Therefore, cooperation between medical care, local governments, and facility that comprehensively supports the living environment of children with FA is needed.

Low-dose-oral immunotherapy for children with wheat-induced anaphylaxis.

BACKGROUND: Oral immunotherapy (OIT) use in patients with wheat anaphylaxis is not well studied. We assessed the efficacy of low-dose OIT for patients with wheat-induced anaphylaxis. METHODS: Eligible subjects were aged 5-18 years with a history of wheat anaphylaxis and confirmed symptoms during oral food challenge (OFC) to 53 mg of wheat protein. After admission to the hospital for a 5-day buildup phase, patients in the OIT group gradually increased wheat ingestion to 53 mg/day and then ingested 53 mg daily at home. One year later, they underwent 53- and 400-mg OFCs after OIT cessation for 2 weeks. The historical control group was defined as patients who avoided wheat during the same period. RESULTS: Median wheat- and ω-5 gliadin-specific immunoglobulin E (sIgE) levels were 293 and 7.5 kUA /L, respectively, in the OIT group (16 children). No patients dropped out. Within 1 year, 88% of patients in the OIT group reached 53 mg. After 1 year, 69% and 9% patients passed the 53-mg OFC and 25% and 0% passed the 400-mg OFC in the OIT and control groups (11 children), respectively (P = .002 and 0.07, respectively). In the OIT group, wheat- and ω-5 gliadin-sIgE levels significantly decreased to 154 and 4.1 kUA /L, respectively, at 1 year, and wheat- and ω-5 gliadin-specific IgG and IgG4 levels significantly increased at 1 month. Anaphylaxis developed 7 times and promptly improved without adrenaline. CONCLUSION: For patients with wheat anaphylaxis, low-dose OIT safely induces immunologic changes, achieves low-dose desensitization, and may allow for a 400 mg dose.

Oral Immunotherapy in Japanese Children with Anaphylactic Peanut Allergy.

BACKGROUND: Reports on oral immunotherapy (OIT) for anaphylactic food allergy are lacking. We investigated the efficacy and safety of peanut OIT for anaphylactic patients. METHODS: We enrolled 22 peanut anaphylactic patients who underwent OIT between 2011 and 2013, all of whom demonstrated anaphylaxis during a baseline double-blind, placebo-controlled food challenge. After starting in-hospital OIT, participants gradually increased ingestion to 795 mg of peanut protein per day at home and then took a maintenance dose (795 mg) daily. After 3 asymptomatic months, participants underwent an oral food challenge (OFC) of 795 mg after 2 weeks of peanut avoidance to confirm sustained unresponsiveness. The historical control group consisted of 11 patients with anaphylaxis by OFC and underwent the second OFC after 2 years. RESULTS: All patients (22/22) achieved desensitization by 8 months after starting OIT and completed the protocol within 2 years. Two years later, 15/22 patients (68.1%) in the OIT group achieved sustained unresponsiveness, whereas only 2 (18.1%) in the control group passed the second OFC. After 2 years, the median peanut-specific IgE had significantly decreased (from 38.5 to 12.4 kUA/L) in the OIT group, but not in the control group. Median peanut- and Ara h 2-specific IgG4 in the OIT group had significantly increased from baseline after 1 month. The adverse reaction rate per ingestion was 43% in hospital and 5% at home. Three patients received adrenaline at the hospital and 2 at home. CONCLUSIONS: These data suggest that for patients with peanut anaphylaxis, OIT can increase the threshold and support achieving sustained unresponsiveness with relative safety.

Predictors of Persistent Wheat Allergy in Children: A Retrospective Cohort Study.

BACKGROUND: Wheat allergy is the third most common food allergy that develops during infancy in Japan. To identify factors associated with persistent wheat allergy, we assessed the rate of tolerance acquisition among Japanese children aged less than 6 years with an immediate-type wheat allergy using the oral food challenge (OFC) method. METHODS: This retrospective cohort study included 83 children (born in 2005-2006) who had a history of immediate-type allergic reaction to wheat and were followed until 6 years of age. The subjects were divided to form "tolerant" (n = 55; tolerance acquired by 6 years of age) and "allergic" (n = 28; tolerance not acquired by 6 years of age) groups based on their OFC results. RESULTS: The rates of tolerance acquisition to 200 g of udon noodles at 3, 5, and 6 years of age were 20.5% (17/83), 54.2% (45/83), and 66.3% (55/83), respectively. The total number of anaphylactic reactions experienced prior to 3 years of age in response to all foods (p < 0.01) and to wheat (p = 0.043) was significantly higher in the allergic than in the tolerant group. Wheat- and ω-5 gliadin-specific immunoglobulin E (IgE) levels were significantly higher in the allergic group than in the tolerant group (p < 0.01), and wheat-specific IgE levels were more likely to increase after infancy in the allergic group. CONCLUSIONS: A history of anaphylaxis to all foods including wheat and/or a high level of wheat- or ω-5 gliadin-specific IgE antibodies were identified as risk factors for persistent wheat allergy.

Specific IgE for Fag e 3 Predicts Oral Buckwheat Food Challenge Test Results and Anaphylaxis: A Pilot Study.

BACKGROUND: Buckwheat (BW) is the source of a life-threatening allergen. Fag e 3-specific serum IgE (sIgE) is more useful than BW-sIgE for diagnosis; however, it is unknown whether Fag e 3-sIgE can predict oral food challenge (OFC) results and anaphylaxis. This study aimed to clarify the efficacy of Fag e 3-sIgE in predicting OFC results and anaphylaxis. METHODS: We conducted a retrospective review of BW- and Fag e 3-sIgE data obtained using the ImmunoCAP® assay system and fluorescent enzyme-linked immunosorbent assay from children who underwent OFC using 3,072 mg of BW protein between July 2006 and March 2014 at Sagamihara National Hospital, Kanagawa, Japan. RESULTS: We analyzed 60 patients aged 1.9-13.4 years (median 6.0 years); 20 (33%) showed objective symptoms upon BW OFC. The patients without symptoms had significantly lower Fag e 3-sIgE than those with non-anaphylactic (p < 0.001) and anaphylactic reactions to BW (p = 0.004). Fag e 3-sIgE was the only tested factor that significantly predicted positive OFC results (odds ratio 8.93, 95% confidence interval 3.10-25.73, p < 0.001) and OFC-induced anaphylaxis (2.67, 1.12-6.35, p = 0.027). We suggest that a threshold Fag e 3-sIgE level of 18.0 kUE/L has 95% probability of provoking a positive reaction to BW. CONCLUSIONS: Fag e 3-sIgE predicted OFC results and OFC-induced anaphylaxis. We further emphasize paying careful attention to the risk of BW OFC-induced anaphylaxis.

Predictors of Persistent Milk Allergy in Children: A Retrospective Cohort Study.

BACKGROUND: Cow's milk (CM) allergy is the second most common food allergy developed during infancy in Japan. To identify predictors of persistent CM allergy, we investigated the tolerance acquisition rate based on an oral food challenge in children under 6 years of age, diagnosed with immediate-type CM allergy. METHODS: This retrospective cohort study included 131 children born in 2005 with a history of immediate allergic reaction to CM, of whom 39 were excluded because of ongoing oral immunotherapy (n = 18) or a lack of follow-up data (n = 21). The 92 remaining participants were followed for 6 years. Tolerance was defined as no adverse reaction to 200 mL of CM and regular intake of milk at home. Subjects were divided into 3 groups based on age at tolerance acquisition: group I (<3 years; n = 31), group II (3-6 years; n = 42), and group III (persistent allergic group; n = 19). RESULTS: Tolerance acquisition rates by 3, 5, and 6 years of age were 32.6% (30/92), 64.1% (59/92), and 84.8% (70/92), respectively. Age at first hospital visit was significantly higher in groups II and III than in group I (p < 0.001). The incidence of anaphylaxis to other foods was also higher in group III than in group I (p = 0.04), as was CM-induced anaphylaxis (p = 0.03). Furthermore, milk and casein-specific immunoglobulin E (IgE) levels were significantly higher in group III than in group II after birth and remained high thereafter (p < 0.05). CONCLUSIONS: The history of anaphylaxis and high milk-specific IgE levels were associated with persistent CM allergy.

Risk Factors and Clinical Features in Cashew Nut Oral Food Challenges.

BACKGROUND: Cashew nuts (CN) are capable of causing severe allergic reactions. However, little has been reported about the details of CN oral food challenges (OFC). METHODS: CN-specific IgE (sIgE) levels were measured for 1 year in 66 patients who underwent an OFC with >3 g CN for diagnosis or confirmation of tolerance acquisition between June 2006 and August 2014. We retrospectively analyzed the OFC and patient background. RESULTS: The median (IQR) age of the 66 patients (48 boys/men and 18 girls/women) was 7.0 years (5.7-8.8). Twelve patients (18.2%) had a positive OFC result; 6 of 8 (75%) patients with a history of an immediate reaction to CN failed the OFC. Anaphylaxis was experienced by 5 of these 12 (42%) patients. A history of an immediate reaction to CN and the CN sIgE levels were significantly different for patients with a positive or negative OFC result (p < 0.01). Among patients without a previous immediate reaction to CN, the 95% positive predictive value (PPV) for the CN sIgE level for a positive OFC result was 66.1 kUA/L. CONCLUSIONS: A history of an immediate reaction to CN and high CN sIgE were risk factors for a positive OFC result. The number of positive OFC results was relatively low, but there was a high probability of anaphylaxis. We should consider the indication of OFC carefully for patients with a history of immediate reactions to CN and avoid OFC for patients without such a history whose CN sIgE values are >66.1 kUA/L (95% PPV).

Follow-up of patients with uncertain symptoms during an oral food challenge is useful for diagnosis.

BACKGROUND: Uncertain symptoms often emerge during an oral food challenge (OFC), and Open-OFCs with those uncertain mild symptoms are ordinarily regarded as positive. Double-blind placebo-controlled food challenges should be conducted to determine these associations. Nevertheless, studies regarding the diagnosis of uncertain food allergy symptoms are lacking. We examined the diagnostic decision for a food allergy based on uncertain symptoms during an Open-OFC. METHODS: We conducted an Open-OFC between August 2005 and April 2012 with 2271 cases who suspected as allergic to hen's eggs, cow's milk, or wheat. For the primary diagnosis, Open-OFCs with obvious symptoms were classified as "positive," no symptoms as "negative," and uncertain, indeterminate symptoms as "uncertain." We encouraged the children in the uncertain group to consume the causative foods at home more than twice; if any definitive symptoms were induced, children were classified as "intolerant," and children without any symptoms were classified as "tolerant," for the final diagnosis. RESULTS: We analyzed 454 uncertain cases excluding 781 positive cases and 1036 negative cases. The symptoms that occurred for the uncertain cases included slight abdominal pain, localized skin rash, and an isolated cough. Of these cases, 362 (79.7%) were considered tolerant at the final diagnosis. Of the intolerant children at the final diagnosis, the induced symptoms at home were not serious. CONCLUSIONS: Monitoring of recurring symptoms following consumption of causative foods at home by patients with uncertain symptoms improves the diagnostic accuracy of an Open-OFC.

Low-dose oral immunotherapy for children with anaphylactic peanut allergy in Japan.

BACKGROUND: Oral immunotherapy (OIT) is a promising treatment for persons with allergy; however, it can also cause adverse allergic reactions. In this study, we investigated the efficacy of low-dose OIT for anaphylactic peanut allergy. METHODS: Twenty-four children (median age, 9.6 years) with anaphylaxis to peanuts were hospitalized for 5 days and then gradually fed increasing amounts of peanut powder up to 133 mg/day. One year later, they underwent an oral food challenge after 2 weeks of peanut avoidance. Those who were asymptomatic after ingesting 795 mg of peanut protein were defined as having achieved sustained unresponsiveness. We measured peanut- and Ara h2-specific immunoglobulin (Ig) E, IgG, and IgG4 levels at 0, 1, 3, 6, and 12 months in the OIT group and at 0 and 12 months in the control group. RESULTS: At baseline, all children in the OIT group and 8 in the control group had a history of anaphylaxis. The median peanut-/Ara h2-specific IgE levels in the OIT and control groups were 55.4/48.6 and 58.2/38.1 kUa/L, respectively. One year later, 8 (33.3%) children in the OIT group exhibited sustained unresponsiveness, while none in the control group did. In the OIT group, the median peanut-specific IgE levels significantly increased to 194.0 kUa/L, after 1 month and then significantly decreased to 57.5 kUa/L at 12 months. Meanwhile, the median peanut- and Ara h2-specific IgG and IgG4 levels increased significantly after 1 month. CONCLUSION: Low-dose OIT induces immunological changes and has the capability of achieving sustained unresponsiveness in children with peanut anaphylaxis.

Increasing specific immunoglobulin E levels correlate with the risk of anaphylaxis during an oral food challenge.

BACKGROUND: Oral food challenges (OFCs) are necessary to diagnose food allergies; however, these tests can cause anaphylaxis. Higher specific immunoglobulin E (sIgE) levels to causative food have been associated with a positive OFC. To date, no data have been found to indicate the factors associated with severe symptoms or anaphylaxis among challenge-positive patients. This study aimed to clarify the association of sIgE with causative foods and anaphylaxis during OFC among the whole study population and challenge-positive patients. METHODS: This cross-sectional study collected symptom and severity data between June 2012 and December 2016 during an open OFC to diagnose food allergy or confirm tolerance acquisition. We analyzed the risk factors for anaphylaxis during OFC. RESULTS: A total of 2272 cases were analyzed (median age: 3.5 years; egg: 1166 cases; milk: 589 cases; wheat: 388 cases; and peanut: 129 cases). Among 979 challenge-positive patients, anaphylactic reactions were observed in 334 cases. A statistically significant association was observed between anaphylaxis during OFC and higher sIgE levels to causative foods (odds ratio: 2.71, 95% confidence interval: 1.94-3.78, for the third compared to the first tertile, P-value for trend <.001). Only gastrointestinal, respiratory, cardiovascular, and neurological symptoms were also statistically significantly associated with higher sIgE levels to causative foods. CONCLUSIONS: The risk of all symptoms, except skin symptoms, during OFCs increased with increasing sIgE levels, and this consequently increased anaphylaxis during OFCs. The mechanism of how sIgE affects the prevalence of gastrointestinal, respiratory, cardiovascular, and neurological symptoms or anaphylaxis is unknown; thus, further study is required.

Skin prick test is more useful than specific IgE for diagnosis of buckwheat allergy: A retrospective cross-sectional study.

BACKGROUND: Buckwheat (BW) is a potentially life-threatening allergen. Usefulness of BW-specific immunoglobulin-E (BW-sIgE) level for diagnosis of BW allergy is controversial, while the skin prick test (SPT) is widely used because of its less invasive procedure and immediate results. However, there are no data comparing usefulness of the SPT and BW-sIgE level. Therefore, our study aimed to clarify efficacy of the SPT for diagnosis of BW allergy. METHODS: This retrospective cross-sectional study evaluated patients who underwent an oral food challenge (OFC) for diagnosis or confirmation of acquired tolerance using 3072 mg of BW protein between July 2006 and April 2014. We then compared the diagnostic performance of BW sIgE and SPT to predict positive OFC results. RESULTS: We analyzed 126 patients aged 2-16 years (median, 7.7 years), 18 (14%) of whom showed positive OFC results. Between patients with positive and negative OFC results, there was no significant difference in BW-sIgE level. However, patients with positive OFC results had a larger SPT wheal diameter. Area under the curve for positive OFC results for BW-sIgE level and SPT wheal diameter were 0.583 and 0.791, respectively. The 5%, 10%, 50%, and 90% positive predictive values of SPT wheal diameter were 2.0 mm, 5.2 mm, 14.7 mm, and 24.1 mm, respectively. CONCLUSIONS: Our study revealed that the SPT was more useful than BW-sIgE level for diagnosis of BW allergy. Thus, an OFC may be avoided if the patient's SPT wheal diameter is at least 24.1 mm.