Specific oral tolerance induction in children with very severe cow's milk-induced reactions. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study. Oral desensitization as a useful treatment in 2-year-old children with cow's milk allergy.
Some children allergic to cow's milk proteins (CMPs) experience exceptionally severe reactions after ingesting only trace amounts of antigen. Avoiding the food and carrying self-injectable epinephrine are the current strategies for their management.
                The aim of this study was to evaluate the safety and efficacy of specific oral tolerance induction (SOTI) for children with severe CMP-induced systemic reactions.
                Ninety-seven children aged 5 years or older with a history of severe allergic reactions and very high CMP-specific IgE levels were selected for a double-blind, placebo-controlled food challenge. Sixty had positive test results to very small amounts of milk and were randomly divided in 2 different groups. Thirty children (group A) immediately began SOTI, whereas the remaining 30 (group B) were kept on a milk-free diet and followed for 1 year.
                After 1 year, 11 (36%) of 30 children in group A had become completely tolerant, 16 (54%) could take limited amounts of milk (5-150 mL), and 3 (10%) were not able to complete the protocol because of persistent respiratory or abdominal complaints. In group B the result of the double-blind, placebo-controlled food challenge performed after a year was positive in all 30 cases (P < .001).
                In this study SOTI was effective in a significant percentage of cases. Orally administered, food-specific immunotherapy appears effective in desensitizing and potentially permanently tolerizing allergic individuals.
                We sought to determine whether milk oral immunotherapy (OIT) is safe and efficacious in desensitizing children with cow's milk allergy.
                Twenty children were randomized to milk or placebo OIT (2:1 ratio). Dosing included 3 phases: the build-up day (initial dose, 0.4 mg of milk protein; final dose, 50 mg), daily doses with 8 weekly in-office dose increases to a maximum of 500 mg, and continued daily maintenance doses for 3 to 4 months. Double-blind, placebo-controlled food challenges; end-point titration skin prick tests; and milk protein serologic studies were performed before and after OIT.
                Nineteen patients, 6 to 17 years of age, completed treatment: 12 in the active group and 7 in the placebo group. One dropped out because of persistent eczema during dose escalation. Baseline median milk IgE levels in the active (n = 13) versus placebo (n = 7) groups were 34.8 kUa/L (range, 4.86-314 kUa/L) versus 14.6 kUa/L (range, 0.93-133.4 kUa/L). The median milk threshold dose in both groups was 40 mg at the baseline challenge. After OIT, the median cumulative dose inducing a reaction in the active treatment group was 5140 mg (range 2540-8140 mg), whereas all patients in the placebo group reacted at 40 mg (P = .0003). Among 2437 active OIT doses versus 1193 placebo doses, there were 1107 (45.4%) versus 134 (11.2%) total reactions, with local symptoms being most common. Milk-specific IgE levels did not change significantly in either group. Milk IgG levels increased significantly in the active treatment group, with a predominant milk IgG4 level increase.
                Milk OIT appears to be efficacious in the treatment of cow's milk allergy. The side-effect profile appears acceptable but requires further study. Cow's milk allergy (CMA) in children is a important problem in medical practice. Oral desensitization has been proposed as a therapeutic approach, but current protocols are time-consuming and impractical.
                To establish a patient-friendly desensitization regimen with weekly up-dosing and to evaluate it in a randomized controlled trial.
                Thirty children with IgE-mediated CMA confirmed by double-blind placebo-controlled food challenge were equally randomized to desensitization with CM or soy milk as control. The weekly up-dosing lasted 18 weeks. The occurrence and severity of reactions after each dose was evaluated, and the desensitization was stopped if severe reactions occurred. Specific IgE and IgG4 levels to CM were measured at baseline, after 8 weeks, and at the end of the study. The double-blind food challenge was repeated once the desensitization was completed or after premature discontinuation.
                Two active and 1 control patient dropped out. Full tolerance to CM (200 mL) was achieved in 10 active patients and partial tolerance in 1. Two active patients discontinued the desensitization after experiencing severe reactions, whereas no reactions occurred in controls, whose sensitivity to CM remained unchanged. A significant increase in specific IgG4 levels was found only in the active group.
                This weekly up-dosing desensitization protocol for CMA performed under medical supervision was effective and reasonably safe and induced consistent immunologic changes.
                Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. Limited published evidence shows oral desensitization to be a potential intervention option for cow's milk protein (CMPs) allergy.
                The aim of this study was to evaluate the safety and efficacy of oral desensitization in 2-year-old children with cow's milk allergy, as a treatment alternative to elimination diet.
                A total of 60 children aged 24-36 months with IgE-mediated allergy to CMPs were included in this multi-center study and were randomized into two groups. Thirty children (group A: treatment group) began oral desensitization immediately, whereas the remaining 30 (group B: control group) were kept on a milk-free diet and followed-up for 1 year.
                After 1-year follow-up period, 90% of the children in group A had become completely tolerant vs. 23% of the children in group B. In group A, cow's milk skin reactivity and serum-specific IgE to milk and casein decreased significantly from the initial assessment, whereas group B showed no significant change after 1 year of follow-up. Twenty-four patients (80%) developed some reaction during the treatment period: 14 children developed moderate reaction (47%) and 10 mild reaction (33%). The most common manifestations were urticaria-angioedema, followed by cough.
                In this study, oral desensitization was found to be effective in a significant percentage of 2-year-old children with cow's milk allergy. Oral desensitization appears to be efficacious as an alternative to elimination diet in the treatment of 2-year-old children with cow's milk allergy. The side-effect profile appears acceptable but requires further study.
                © 2011 Blackwell Publishing Ltd.
Studies to date have involved small numbers of patients and the quality of evidence is generally low. The current evidence shows that MOIT can lead to desensitization in the majority of individuals with IMCMA although the development of long-term tolerance has not been established. A major drawback of MOIT is the frequency of adverse effects, although most are mild and self-limited. The use of parenteral epinephrine is not infrequent. Because there are no standardized protocols, guidelines would be required prior to incorporating desensitization into clinical practice.