Original article
Intervention
Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study

https://doi.org/10.1016/j.anai.2010.03.015Get rights and content

Background

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.

Objectives

To establish a patient-friendly desensitization regimen with weekly up-dosing and to evaluate it in a randomized controlled trial.

Methods

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.

Results

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.

Conclusions

This weekly up-dosing desensitization protocol for CMA performed under medical supervision was effective and reasonably safe and induced consistent immunologic changes.

Introduction

Among food allergies, cow's milk allergy (CMA) is the most relevant in the pediatric age group owing to its prevalence, the practical difficulties in management, the emotional burden for children and parents, and the nutritional implications. Currently, the management of CMA is primarily based on the complete avoidance of CM. This approach is associated with impaired quality of life for allergic children and their families.1, 2 In addition, it is difficult to achieve complete avoidance because milk proteins can be present in small amounts or even as hidden allergens in a variety of processed foods. This may lead to unexpected exposure and possibly severe reactions. The present interventions for CMA include avoidance maneuvers and education regarding the proper indications for and use of autoinjectable epinephrine. Among the CM substitutes most frequently used are soy formulas and extensively hydrolyzed formulas of casein and whey. These substitutes have an acceptable nutritional value, but hydrolyzed formulas often have an unpleasant taste and are expensive and soy formulas have themselves the potential to evoke allergic reactions.

It has been shown that infants with CMA but without detectable specific IgE levels to CM have a higher spontaneous recovery rate compared with infants with high levels of specific IgE toward milk proteins (IgE-mediated CMA).3, 4, 5 Oral desensitization or immunotherapy, also referred to as “tolerance induction,” has been suggested as a suitable approach to reduce clinical symptoms and modify the immune response to allergens, and this was also confirmed in the case of CMA.6, 7, 8, 9, 10, 11 Oral immunotherapy is usually performed starting with very low amounts of milk, which are then slowly increased until an amount comparable with the usual daily intake is reached. Afterward, milk is given daily to maintain the tolerant state. The protocols that have been published usually have a very long duration6, 12 or require hospitalization of the child for several days.6, 7 As such, they are considered, to some extent, to be impractical. Based on these considerations, we attempted to set up a more patient-friendly and easy-to-perform oral desensitization using a weekly up-dosing regimen. The feasibility of this approach was demonstrated in a previous open exploratory study.13 The present trial was undertaken to confirm in a randomized and controlled manner the clinical efficacy and safety of this approach.

Section snippets

Overall Design

This study was designed as a randomized, single-blind, soy milk–controlled trial with 2 parallel groups. Children 4 years or older with demonstrated IgE-mediated CMA were enrolled and were randomized to receive either active oral immunotherapy or matched soy formula. The efficacy of the desensitization was evaluated during a 4-month period by identifying the maximum tolerated dose of milk or, ideally, 200 mL. The ethics committee of the Department of Pediatrics, University of Messina, approved

Clinical Results

The disposition of all patients considered for the study is summarized in Figure 1. Thirty children who fulfilled the inclusion and exclusion criteria were enrolled in the study and were equally randomized to active desensitization or control intervention. The clinical characteristics of the participants at randomization are given in Table 2. There were 2 dropouts in the active group and 1 in the control group (their parents withdrew their consent early in the study for personal reasons and not

Discussion

There is currently no specific curative treatment available for IgE-mediated food allergy, for which total avoidance of the offending food is the only effective approach. It was previously suggested that CMA tends to disappear in older age in most children and that approximately 85% of patients become tolerant by age 3 years. However, more recent studies14, 15 provided a less optimistic view. The burden of the disease and its tendency to persist across time in some individuals highlight the

Acknowledgment

We thank Dr Harold Nelson for revising the English language of the manuscript and for his helpful comments and suggestions.

References (22)

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    A protocol for oral desensitization in children with IgE-mediated cow's milk allergy

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    Disclosures: Authors have nothing to disclose.

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