Ken-ichi Nagakura

Safety and Efficacy of Low-Dose Oral Immunotherapy for Hen's Egg Allergy in Children

Background: The minimal dose for oral immunotherapy (OIT) tolerance is unknown. We investigated the efficacy and safety of low-dose OIT with 1/32 of the volume of a whole egg. Methods: Thirty-three children (aged ≥5 years) with egg allergies confirmed by oral food challenge against 1/32 of a heated whole egg (194 mg of egg protein) were enrolled. The OIT group ingested a scrambled egg once a day. The volume was gradually increased up to a maximum of 1/32 of a heated whole egg. Egg consumption was completely absent in the control group. Results: There were no significant differences in background between the OIT and control groups. Respectively, 71% (15/21) and 0% (0/12) of the patients in the OIT and control groups exhibited sustained unresponsiveness to 1/32 of a whole egg 2 weeks after stopping OIT after 12 months (p < 0.001); 33% (7/21) and 0% (0/12; p = 0.032), respectively, showed sustained unresponsiveness to 1/2 of a whole egg. Egg white- or ovomucoid-specific IgE levels in the OIT group were significantly lower than at baseline after 12 months. Egg white- or ovomucoid-specific IgG as well as IgG4 levels in the OIT group were significantly higher than baseline levels after 1, 3, 6, and 12 months. Adverse allergic reactions were rare, and most symptoms were mild. Conclusions: Low-dose OIT induced sustained unresponsiveness to 1/32 and 1/2 of a whole egg, with no severe symptoms. To improve food allergies, continuous intake of small amounts of these foods may be as effective as the consumption of larger quantities.

Oral immunotherapy initiation for multi-nut allergy: a case report.

Oral immunotherapy (OIT) has been reported to be effective for food allergy in recent years,1 but most studies on OIT have focused on a single antigen. Begin et al. first reported the use of OIT using peanuts and another allergen simultaneously, which was feasible and relatively safe.2 The purpose of this study was to evaluate the safety and efficacy of multi-nut OIT initiation for a patient with multi-nut allergy. We enrolled a 22-year-old man who had peanut, cashew nut, andwalnut allergies. He experienced face swelling after eating peanuts at the age of one. He and his mother tried to eliminate peanuts and other nuts completely; however, he occasionally ingested nuts accidentally. He had conjunctival erythema, lip swelling, and a cough after peanut ingestion at the age of 17 and generalized flushing, vomiting, and breathing difficulty after cashew nut ingestion at the age of 21. He was initially checked for food-specific IgE (sIgE) and component-resolved diagnostics (CRD) using the ImmunoCAP assay system (Thermo Fisher Scientific, Uppsala, Sweden). Food sIgE (kU/l) was 11.6 for peanut, 3.87 for cashew nut, 6.08 for walnut, 5.92 for pistachio, 2.22 for macadamia nut, and <0.10 for almond and hazel nuts. CRD was 0.24 for Ara h 1, 13.6 for Ara h 2, 7.34 for Ana o 3, <0.10 for Ara h 3, 8, and 9, Jug r 1 and 3, Bet v 1 and 2, Pru p 3, and Gly m 4, 5, and 6. Open oral food challenge of 0.5 g of peanut or 3.0 g of each nut was conducted before OIT. Peanut was administered at 60-min intervals as follows: 1/4 and 3/4. Each nut was administered at 30-min intervals as follows: 1/8, 3/ 8, and 4/8. He reacted to 0.5 g of peanut, 1.1 g of cashew nut, and 3.0 g of walnut. He tolerated pistachio, macadamia nut, almond, and hazel nut. He received OIT using peanut, cashew nut, and walnut simultaneously. From the day of admission, he took loratadine (10 mg) before nut intake. On the day of admission, a double-blind, placebo-controlled food challenge (DBPCFC) was performed. The challenge food was made by mixing equal amounts of the three nuts. From the second to fourth day in the hospital, he ingested mixed nut powder, which contained equal amounts of the three nuts, twice a day. During his stay, we adjusted the amount so that he would not experience severe symptoms at home. After discharge, he took the same amount once a day after taking loratadine. We investigated the severity of symptoms for safety and changes in symptom occurrence and food sIgE for efficacy. This study was approved by the Sagamihara National Hospital Ethics Committee

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.

Reactions of Buckwheat-Hypersensitive Patients during Oral Food Challenge Are Rare, but Often Anaphylactic

Background: Buckwheat (BW) is a common cause of life-threatening allergy in Asia. Few have examined oral food challenges (OFCs) using BW. We here describe the OFC outcomes for the diagnosis or confirmation of tolerance acquisition and clarify risk factors for positive OFCs. Methods: Between July 2005 and March 2014, we retrospectively reviewed data from children who underwent OFCs using 3,072 mg of BW protein at Sagamihara National Hospital. Children were suspected of having BW allergy because of positive results for BW-specific IgE or because they had been previously diagnosed with BW allergy owing to immediate reactions to BW. Results: Of 476 such patients, we analyzed 419 aged 1-17 years (median age 6.7 years). Forty-four (10.5%) reacted to the BW OFC and 24 (54.5%) experienced anaphylaxis. Among patients with suspected BW allergies (n = 369), 30 (8.1%) reacted to OFC. However, among patients with definitive BW allergies (n = 50) who underwent OFCs a median of 7.0 years after their last immediate reaction, 14 (28.0%) reacted to OFC. Among 12 patients with past anaphylactic reactions to BW, 8 exhibited tolerance to BW. A history of immediate reaction to BW and high BW-specific IgE levels were significant risk factors for a positive OFC. Conclusions: BW allergies are rare among children suspected of having BW allergies due to positivity for BW-specific IgE. Most children with definitive BW allergies can tolerate BW, even after anaphylactic reactions. Nevertheless, careful observation is needed when performing BW OFCs, considering the high incidence of anaphylactic reactions.

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

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.

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.

Novel immunotherapy and treatment modality for severe food allergies

Purpose of review In recent years, many studies on oral immunotherapy (OIT) have been conducted; however, few have focused on severe food allergies. The purpose of this review was to assess the efficacy and safety of oral immunotherapies for patients with severe food allergy. Recent findings We reviewed multiple immunotherapy reports published within a few years or reports focusing on severe food allergies. We also investigated recent studies on OIT and novel food allergy management. Summary Immunotherapies targeting low-dose antigen exposure and oral food challenges using low-dose target volumes may be safer than conventional OIT. It is necessary to consider which immunotherapy regimen is appropriate based on allergy severity of the patient.