Accidental allergic reactions to immediate-type food allergens in Japanese children: A single-center study.

BACKGROUND: Few studies have assessed the nature of accidental allergic reactions (AAR). We assessed the prevalence and risk factors for AAR in Japanese children. METHODS: This study included children with immediate-type hen's egg (HE), cow's milk (CM), wheat, or peanut allergy who developed allergic reactions within at least 2 years and were followed up regularly at a single national allergy center in Japan. From January to December 2020, low-dose reactivity was defined as allergic reactions to ≤250, ≤102, ≤53, or ≤ 133 mg of HE, CM, wheat, or peanut protein, respectively. The annualized AAR rate showed the number of reactions per patient per year (95% confidence interval). AAR risk factors were analyzed using multiple logistic regression. RESULTS: Of the 1096 participants, 609, 457, 138, and 90 had HE, CM, wheat, and peanut allergies, respectively. The median (interquartile range) age was 5.0 (2.3-8.6) years, 39% had completely eliminated allergenic food, and 24% had low-dose reactivity. The annualized AAR rate was 0.130 (0.109-0.153) in all sub-cohorts. Moderate and severe symptoms occurred in 50% and 0.7%, respectively, of children who experienced AAR. Multiple logistic regression revealed that low-dose reactivity was a significant risk factor for AAR in the overall and CM cohorts, respectively (p < .001 and p = .036). CONCLUSION: In this single-center study in Japan, the annualized AAR rate was relatively low during the COVID-19 pandemic; however, half of the participants with AAR had moderate to severe symptoms. Especially in the case of low-dose reactivity, children would require careful AAR risk management.

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.

[DEVELOPMENT AND VALIDATION OF QUALITY OF LIFE QUESTIONNAIRE FOR PARENT BURDEN OF CHILDREN WITH FOOD ALLERGY].

OBJECTIVE: Quality of life (QOL) questionnaires for parents of children with food allergies have been developed in the United States and Europe. However, no original Japanese QOL questionnaire has been developed till date. We aimed to develop an original questionnaire to evaluate the QOL in parents of children with food allergies in Japan. METHODS: We collected QOL-related questions from parents of children with food allergies aged 0-15 years, and created a primary questionnaire. Responses to the primary questionnaire were obtained from the parents again, and question items were reduced using factor analysis to create a secondary questionnaire comprising eight items. In addition to the secondary questionnaire, responses to the Food Allergy QOL Questionnaire-Parent Form (FAQLQ-PF) Japanese version, Parent reported Health-Related QOL in children and adolescents (KINDL) and Health-related QOL (SF-8) were obtained from parents to assess the validity of the secondary questionnaire. RESULTS: A total of 407 parents completed all questionnaires. The secondary questionnaire scores were positively correlated with those of FAQLQ-PF and weakly negatively correlated with the KINDL and SF-8 mental component summary scores. Parents of children with food allergies with ≥3 culprit foods or severe reactions to daily foods, a history of anaphylaxis, and those carrying adrenaline autoinjectors scored higher and had lower QOL. CONCLUSION: The developed original questionnaire is a valid QOL questionnaire for Parents of children with food allergies.

Natural history of cow's milk allergy in children aged 6-12 years.

BACKGROUND: Approximately 50%-90% of children with immediate-type cow's milk allergy (CMA) acquire tolerance by pre-school age. We aimed to investigate the acquisition rate of CMA tolerance in children aged 6-12 years. METHODS: We included children with CMA who persisted until the age of 6. Tolerance was defined as passing an oral food challenge with 200 mL of unheated cow's milk (CM) or consuming 200 mL of CM without symptoms, whereas persistent CMA was defined as fulfilling neither of these criteria by 12 years old. Children receiving oral immunotherapy (OIT) were excluded from the primary analysis. Risk factors associated with persistent CMA were assessed using Cox regression analysis. RESULTS: Of 80 included children, 30 (38%) had previous CM anaphylaxis, and 40 (50%) had eliminated CM completely from their diet. The median CM-specific immunoglobulin E (sIgE) level at 6 years old was 12.0 kUA /L. Tolerance was acquired by 25 (31%) and 46 (58%) children by the age of 9 and 12 years, respectively. At baseline, persistent CMA was associated with higher CM-sIgE levels (hazard ratio 2.29, 95% confidence interval 1.41-3.73, optimal cutoff level 12.7 kUA /L), previous CM anaphylaxis (2.07, 1.06-4.02), and complete CM elimination (3.12, 1.46-6.67). No children with CMA who had all three risk factors (n = 14) acquired tolerance. CONCLUSION: Except for OIT patients, more than half of children with CMA at 6 years old acquired tolerance by 12 years old. Children with CMA who have the risk factors are less likely to acquire tolerance.

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.

Analysis of drug-induced anaphylaxis cases using the Japanese Adverse Drug Event Report (JADER) database - secondary publication.

BACKGROUND: The epidemiology of drug-induced anaphylaxis using the Japanese nationwide database has been not reported, even though drugs are a common trigger of anaphylaxis. The aim of this study was to describe the epidemiological profile of cases of drug-induced anaphylaxis, including fatal cases, using the data from the Japanese Adverse Drug Event Report database (JADER). METHODS: We extracted data regarding drug-related adverse events, between April 2004 and February 2018, published in JADER by the Pharmaceuticals and Medical Devices Agency. We analyzed cases of anaphylaxis occurring between January 2005 and December 2017. The drug classification was based on the Japanese Standard Commodity Classification. RESULTS: There were 16,916 cases of anaphylaxis reported during the study period. Among them, 418 fatalities were registered. The incidence of drug-induced anaphylaxis and fatal cases was 1.03 cases/year per 100,000 population and 0.03 cases/year, respectively. The most frequent causes of anaphylaxis were diagnostic agents, including X-ray contrast media (20.3%), and biological preparations, such as human blood preparations (20.1%). In fatal cases, diagnostic agents (28.7%) and antibiotic preparations (23.9%) were the most commonly associated types of drugs. CONCLUSIONS: The frequency of drug-induced anaphylaxis and fatalities in Japan remained unchanged over the 13-year period analyzed in this study. Diagnostic agents and biological preparations were the most frequent causes of anaphylaxis; however, fatalities were most frequently caused by either diagnostic agents or antibiotic preparations.

Current situation of anaphylaxis in Japan: Data from the anaphylaxis registry of training and teaching facilities certified by the Japanese Society of Allergology - secondary publication.

BACKGROUND: Anaphylaxis is a potentially fatal severe systemic hypersensitivity reaction that causes symptoms in multiple organs such as the skin, respiratory tract, and gastrointestinal tract; however, no nationwide epidemiological survey on anaphylaxis has been conducted in Japan. This survey aimed to elucidate the triggers and treatment of anaphylaxis in Japan. METHODS: Between February 2015 and October 2017, we prospectively collected clinical data on the triggers and treatment of patients who developed anaphylaxis or were admitted to the emergency room with anaphylaxis in the training and teaching facilities of the Japanese Society of Allergology. RESULTS: This study included 79 of the 451 affiliated facilities (18%), and a total of 767 patients were enrolled; 73% of them were aged <18 years and 7% had in-hospital triggers. The most common triggers were food (68%), drugs (12%), food-dependent exercise-induced anaphylaxis (5%), insects (4%), and oral immunotherapy (3%), with drugs being the most common in-hospital trigger and food being the most common out-of-hospital trigger. Intramuscular injection of adrenaline was administered therapeutically to 38% of the patients, with 10% requiring multiple doses. Adrenaline auto-injectors were used in 12% of out-of-hospital patients. CONCLUSIONS: The present survey revealed the most common triggers and treatments for anaphylaxis in Japan. Self-management and adrenaline administration as first-line treatment may not be done sufficiently. Therefore, it is necessary to thoroughly educate and train patients and physicians about anaphylaxis.

[JAPANESE TRANSLATION AND LINGUISTIC VALIDATION OF THE RECAP OF ATOPIC ECZEMA (RECAP)].

BACKGROUND: The Recap of atopic eczema (RECAP), a new core outcome of the atopic dermatitis trial, was translated into Japanese and linguistically validated. METHODS: Translation into Japanese was accomplished according to the ISPOR (International Society for Pharmacoeconomics and Outcome Research) guidelines and the basic guidelines for scale translation. The translation process included two forward translations, reconciliation with native English speakers, third-party back translation, cognitive debriefing, review and harmonization by the original authors. Twenty-seven atopic dermatitis and pediatric specialists from 21 centers in Japan participated in the translation process. Cognitive debriefing was conducted through face-to-face interviews using a think-aloud method with the interview guide including questions about comprehensibility, relevance, comprehensiveness, recall period and suggested improvements, based on the COSMIN methodology. RESULTS: No linguistic or cultural problems were encountered in the translation into Japanese. Cognitive debriefings were conducted with 10 adult patients and 10 parents of pediatric patients. Some minor modifications were made following discussion and approval by the research team and the original authors. The Japanese version of RECAP was considered to be understandable, comprehensive and relevant for adult patients and families of pediatric patients. CONCLUSION: The Japanese version of the RECAP, which has been validated as linguistically equivalent to the original version, is now available. Further evaluation of the measurement properties is needed in the future.

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.

Cross-reactivity of each fraction among cereals in children with wheat allergy.

BACKGROUND: Cross-reactivity between wheat and other cereals is a crucial issue in the management of wheat allergy. Few studies have reported in vitro cross-reactivity in immediate-type wheat allergy. The aim of this study aimed to examine cross-reactivity of the three fractions (albumin/globulin, gliadin, and glutenin fractions) among cereals in children with wheat allergy. METHODS: Sera from 128 children with immediate-type wheat allergy were collected. Specific immunoglobulin E (sIgE) levels against each fraction of wheat, barley, and rye were measured by enzyme-linked immunosorbent assay (ELISA). Cross-reactivities of each fraction among wheat, barley, and rye were examined via inhibition ELISA. RESULTS: All subjects were sensitized to all fractions of wheat, barley, and rye. The wheat sIgE levels were significantly higher than those of barley and rye in all the fractions (p ≤ .001) and were significantly correlated with sIgE levels in each fraction (r = .887-.969, p < .001). Inhibition ELISA revealed that wheat inhibited the IgE binding to most of the solid phases at lower protein levels compared with barley and rye in all fractions. CONCLUSIONS: In children with immediate-type wheat allergy, sensitization to all the three fractions of wheat was observed. In addition, they showed sensitization to barley and rye caused by in vitro cross-reactivity with wheat in each fraction. When managing children with wheat allergy, sensitization to barley and rye caused by the cross-reactivities should be considered.

Clinical cross-reactivity of wheat and barley in children with wheat allergy.

BACKGROUND: Several studies have reported in vitro cross-reactivity between wheat and barley. However, evidence regarding the clinical cross-reactivity of wheat and barley is limited. This study examined the clinical cross-reactivity of barley and wheat among children with immediate-type wheat allergies. METHODS: We examined the threshold dose of a wheat oral food challenge for wheat-allergic children. We examined the reactivity of barley, and the oral food challenges of barley tea and barley rice were implemented as needed. We measured the specific immunoglobulin E (sIgE) levels in wheat, ω-5 gliadin, and barley. RESULTS: We evaluated 53 children (39 [74%] boys) with a median age of 6.6 years. Among them, 39 (74%) patients had a history of anaphylaxis to wheat. The median wheat-, barley-, and ω-5 gliadin-sIgE levels were 57.3, 12.1, and 3.2 kUA /L, respectively. Twelve patients reacted to barley tea (1.8 mg), 14 reacted to barley rice (220-440 mg), and 27 were tolerant to barley tea and barley rice. Barley-allergic patients had significantly higher wheat- and ω-5 gliadin- and barley-sIgE levels and significantly lower threshold doses of wheat than barley-tolerant patients. Omega-5 gliadin-sIgE was the most useful predictor of barley allergy among wheat-allergic patients; the ω-5 gliadin-sIgE 95% positive predictive value for barley allergy was 4.6 kUA /L. CONCLUSIONS: Half of wheat-allergic children reacted to barley. A lower threshold dose of wheat is related to cross-reactive barley allergies. Omega-5 gliadin-sIgE predicts cross-reactive barley allergy in children allergic to wheat. Clinical cross-reactivity to barley should be considered in the management of wheat-allergic children.

Macadamia nut-specific IgE levels for predicting anaphylaxis.

BACKGROUND: Despite the high risk of anaphylaxis in patients with a macadamia nut allergy (MdA), little is known about the significance of macadamia nut-specific immunoglobulin E (Md-sIgE). Thus, this study aimed to investigate the utility of Md-sIgE for predicting anaphylaxis. METHODS: Children with suspected MdA who visited our hospital were included. MdA was defined as either failing the 3-g macadamia nut (Md) oral food challenge (OFC) or confirming obvious immediate symptoms following Md ingestion. Non-MdA was defined as passing the 3-g Md OFC. RESULTS: A total of 41 children (29 [71%] males) with a median age of 7.7 years were included. The median Md-sIgE level was 2.23 kUA /L. Among the 21 children diagnosed with MdA, eight and 13 children did (An group) and did not (non-An group) develop anaphylaxis. Twenty children were included in the non-MdA group. The Md-sIgE level was significantly higher in the An group relative to the others (7.97 vs. 1.92 kUA /L, p < .001). Furthermore, the Md-sIgE level was significantly higher in the An group than in the non-An group (7.97 vs. 1.92 kUA /L, p = .02). However, there was no significant difference in the Md-sIgE between the non-An and non-MdA groups (1.92 vs. 1.90 kUA /L, p > .99). The area under the curve for predicting anaphylaxis in Md-sIgE was 0.92 (95% CI: 0.83-1.00), and the optimal cut-off value was 3.76 kUA /L. CONCLUSION: Md-sIgE levels were useful in predicting anaphylaxis. Above the cut-off value, we emphasize paying careful attention to the risk of anaphylaxis.

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.

[ANALYSIS OF DRUG-INDUCED ANAPHYLAXIS CASES USING THE JAPANESE ADVERSE DRUG EVENT REPORT DATABASE].

BACKGROUND: The epidemiology of drug-induced anaphylaxis (AN) using the Japanese nationwide database has not been reported, even though drugs are a common trigger of AN. OBJECTIVE: This study aimed to describe the epidemiological profile of drug-induced AN, including fatal cases, using the Japanese Adverse Drug Event Report database (JADER). METHODS: We extracted data regarding drug-induced adverse events between April 2004 and February 2018 published in JADER by the Pharmaceuticals and Medical Devices Agency. We analyzed cases of anaphylaxis occurring between January 2005 and December 2017. The drug classification was based on the Japanese Standard Commodity Classification. RESULTS: There were 16916 cases of anaphylaxis reported during the study period. Among them, 418 fatalities were registered. The incidence of drug-induced AN and fatal cases was 1.03 cases/year per 100000 population and 0.03 cases/year, respectively. The most frequent causes of AN were diagnostic agents including X-ray contrast media (20.3%) and biological agents including human blood preparations (20.1%). In fatal cases, diagnostic agents (28.7%) and antibiotics (23.9%) were the most frequent causes. CONCLUSIONS: The frequency of drug-induced AN and fatalities in Japan remained unchanged over the 12-year period analyzed in this study. Diagnostic and biological agents were the most frequent causes of AN. Contrarily, fatalities were most frequently caused by diagnostic and antibiotic agents.

[CURRENT SITUATION OF ANAPHYLAXIS IN JAPAN: DATA FROM THE ANAPHYLAXIS REGISTRY OF TRAINING AND TEACHING FACILITIES CERTIFIED BY THE JAPANESE SOCIETY OF ALLERGY].

BACKGROUND: No nationwide epidemiological survey of anaphylaxis in Japan has been conducted. The aim of this study was to elucidate the triggers and treatment of anaphylaxis in Japan. METHODS: We prospectively collected clinical information on the triggers and treatment of patients who developed anaphylaxis or were admitted to the emergency room with anaphylaxis in the training and teaching facilities of the Japanese Society of Allergology between February 2015 and October 2017. RESULTS: Seventy-nine of 451 facilities (18%) participated in the study, and a total of 767 patients (under 18 years, 73%; in-hospital, 7%) were enrolled. The most common triggers were food (68%), drugs (12%), food-dependent exercise-induced anaphylaxis (5%), insects (4%), and oral immunotherapy (3%), with drugs being the most common in-hospital trigger and food being the most common out-of-hospital trigger. The intramuscular injection of adrenaline in medical institutions accounted for 38% of cases, 10% of which required multiple doses. The rate of use of adrenaline self-injections in out-of-hospital cases was 12%. CONCLUSION: The present study revealed the most common triggers and treatment for anaphylaxis in Japan. Self-management at the onset of anaphylaxis and adrenaline administration as the initial treatment may be insufficient. Therefore, it is necessary to thoroughly instruct patients and educate physicians regarding anaphylaxis.

Formation of IgE-Allergen-CD23 Complex Changes in Children Treated with Subcutaneous Immunotherapy for Japanese Cedar Pollinosis.

BACKGROUND: Subcutaneous immunotherapy (SCIT) is used to treat Japanese cedar (JC) pollinosis. The formation of IgE-allergen-CD23 complex after SCIT for JC pollinosis has not yet been fully elucidated. OBJECTIVE: The objective of this study was to investigate the formation of IgE-allergen-CD23 complex after SCIT for JC pollinosis. METHODS: Eleven patients were treated with 3-year SCIT for JC pollinosis at Sa-gamihara National Hospital from 2013 to 2014. Nasal and ocular symptoms (in terms of symptom scores) during the scattering of JC pollen and immunological changes were investigated. Levels of JC pollen-specific antibodies (IgE and IgG4) were measured by ImmunoCAP assays. To detect the changes in allergen-presenting ability of B cells, the levels of IgE-allergen-CD23 complexes in serum were measured by a cell-free, enzyme-linked immunosorbent-facilitated antigen-binding assay. RESULTS: The median (interquartile range) age of the subjects was 8 (6-10) years. Three patients (27%) had comorbid atopic dermatitis, and 5 patients (45%) had comorbid bronchial asthma. Before starting SCIT, the total IgE level was 373 (75-2,870) kU/L, and the level of JC pollen-specific IgE was 77.2 (15.4-528) kUA/L. Symptom scores improved significantly from the year after treatment. JC pollen-specific IgE levels did not change after 3 years of treatment. JC pollen-specific IgG4 levels increased significantly throughout the treatment period. The levels of IgE-allergen-CD23 complexes decreased significantly after 3 years of treatment. CONCLUSION: The ability of IgE-allergen complexes to bind to CD23 decreased after SCIT, suggesting that increasing levels of IgE-blocking antibodies, including IgG4, may play an important role in the mechanism of SCIT.

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.

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.

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.