No abstract

Background: Severe anaphylactic symptoms can occur during oral food challenges (OFCs). Thus, high-risk patients (e.g., patients with a history of anaphylaxis or high antigen-specific immunoglobulin E [IgE] levels) must carefully undergo OFCs in hospitals. We attempted to identify the risk factors for severe symptoms during OFC testing among high-risk patients. Methods: We retrospectively evaluated patients' characteristics and severe symptoms that were experienced during a double-blind placebo-controlled food challenge test performed before the patients underwent oral immunotherapy between June 2008 and June 2012. Patients were ≥5 years old and had an anaphylactic history or antigen-specific IgE (>30 kUA/L). Severe symptoms were defined using the grading of the Japanese Anaphylaxis Guidelines, which are modified from the European Academy of Allergology and Clinical Immunology Guidelines. Results: We evaluated 393 cases with positive test results, including 98 cases with severe symptoms. The most frequent severe symptoms were respiratory (77%), gastrointestinal (28%), cardiovascular (27%), and neurological (13%) symptoms. Multivariate analysis revealed that the significant factors for a severe reaction were a history of anaphylaxis to the causative food (adjusted odds ratio [OR]: 2.147, p = 0.003), older age (per 1 year increase, adjusted OR: 1.102, p = 0.044), and an egg OFC (adjusted OR: 0.433, p = 0.003). Conclusions: The risk factors for a severe reaction to OFCs were a history of an anaphylactic reaction and older age. An egg OFC was associated with low risk of severe symptoms during OFC. Therefore, OFCs for patients with these risk factors should only be performed under specialist supervision with access to rapid treatment and full resuscitation equipment.

Background: This study aimed to investigate the efficacy and safety of low-dose-induction oral immunotherapy (OIT) with 3 ml of milk, which is a lower target volume than is conventionally used. Methods: Children aged ≥5 years with milk allergies [confirmed by oral food challenge (OFC) against 3 ml of milk] were enrolled. The OIT group was admitted to the hospital for 5 days for build-up. Subsequently, at home, the volume was gradually increased by up to a maximum of 3 ml every 5 days. While the OIT group ingested a small amount of milk every day, the control group completely eliminated their milk intake. Both groups underwent OFCs approximately 1 year later in order to assess their responsiveness to 3 ml and 25 ml of cow's milk. Results: The OIT and control groups had no background differences; the proportion of patients unresponsive to 3 ml of milk after 1 year was 58.3% (7/12) and 13.8% (4/25), respectively (p = 0.018), while the proportion unresponsive to 25 ml of milk was 33.3% (4/12) and 0.0% (0/25), respectively (p = 0.007). Furthermore, a significant decrease in the casein-specific immunoglobulin E levels was seen after 12 months when compared to baseline in the OIT group (p = 0.033). Adverse allergic reactions were rare and most symptoms were mild. Conclusion: This study of a high-risk population reacting to very low amounts of milk showed that low-dose-induction OIT appeared effective for acquiring unresponsiveness to 3 ml and 25 ml of milk, with severe symptoms being rare, indicating that for improvement of food allergies, continuous intake of small amounts may be as effective as intake of larger amounts.

Low-dose OIT induces immunological changes and has the capability of achieving sustained unresponsiveness in children with peanut anaphylaxis.

The group III experienced HE-related anaphylaxis and complications more frequently and exhibited sustained, high EW- and OM-specific IgE levels.

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.

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.

Oral immunotherapy (OIT) is a significant focus of treatment of food allergy. OIT appears to be effective in inducing desensitization, however, patients receiving OIT frequently developmild/moderate symptoms during the therapy. It has not been clearly established whether the clinical tolerance induced by OIT resembles natural tolerance. According to our data, the efficacy of OIT is different among food antigens, and it is comparatively difficult to achieve the clinical tolerance in milk OIT. Moreover, the definitive evidence of efficacy and safety with long-term therapy is limited. Further studies need to be offered to patients in clinical practice. Recently, novel treatments for food allergy, sublingual and epicutaneous immunotherapy, and combination treatment with an anti-IgE monoclonal antibody (omalizumab), have been examined in some studies. OIT combined with omalizumab increased the threshold doses of food without adverse reactions and may be of benefit in food allergy treatment. More studies are needed to demonstrate long-term safety and treatment benefits in a larger patient cohort.