Peanut allergy is a worldwide concern, but especially in Western countries, in which prevalence has doubled in the last ten years, to a rate of 1.4 to 3.0 percent of children. To prevent the development of peanut allergy, national guidelines have attempted to keep pace with this crisis, with recommendations, at first, of delayed exposure to peanut and, more recently, of earlier exposure. But a universally accepted and research-supported approach to the prevention of peanut allergy remains elusive.
The New England Journal of Medicine published a landmark study about the prevention of peanut allergy. The selection criteria for the 640 infants who were included in the trial were very strict:
- age of at least 4 months and younger than 11 months
- presence of severe eczema, egg allergy, or both conditions
These infants were then skin tested to peanut and were assigned to one of two groups. The first group consisted of infants with no measurable wheal upon testing and the second group consisted of infants with wheals measuring 1 to 4 mm in diameter. These infants were then randomly assigned to consume peanuts or avoid peanuts until age 60 months. The infants who were randomly assigned to consume peanut underwent a baseline, open-label food challenge in which those who had had negative results on the skin test were given 2 g of peanut protein in a single dose and those who had positive skin test results were given incremental doses up to a total of 3.9 g. Those infants who did not have a reaction to the baseline challenge were fed at least 6 g of peanut protein per week (divided between three or more meals), while those infants who did have a reaction to the baseline challenge were instructed to avoid peanuts. Note that the infants who had a reaction to the baseline challenge were still included in the intention-to-treat analysis. The primary outcome measure was the proportion of infants with peanut allergy at age 60 months. This primary outcome was determined, in 617 infants, by means of an oral challenge to peanut. The investigators also measured and reported peanut-specific levels of IgG4 and IgE antibody.
Here is what was found:
- In the 542 infants with negative results on initial skin testing, prevalence of peanut allergy was:
- 1.9 percent in the peanut consumption group
- 13.7 percent in the peanut-avoidance group
- In the 98 infants with positive results on initial skin testing, prevalence of peanut allergy was:
- 10.6 percent in the peanut consumption group
- 35.3 percent in the peanut-avoidance group
These results represent an 86.1 percent and 70.0 percent relative reduction in the prevalence of peanut allergy in the negative skin test and positive skin test groups, respectively.
Of the 57 infants (now 60-month-old children) who had a positive oral challenge to peanut at the end of the study, 14 had respiratory or cardiovascular signs and 9 received intramuscular epinephrine.
With regard to immunologic assessments, the investigators found that levels of peanut-specific IgG4 increased over time in both the consumption group and the avoidance group. However, these changes were significantly larger in the consumption group. The ratio of peanut-specific IgG4:IgE increased in the consumption group but was relatively constant in the avoidance group. These findings are important because, while IgE is the antibody type primarily involved in allergic sensitization and allergic reactions, IgG4 has some blocking or attenuating effects on IgE and, therefore, is associated with less allergy.
In the 17 years I have been in practice as an allergist-immunologist, this is the most exciting advance in the field of food allergy. This study showed that, in carefully selected and screened infants, the rate of peanut allergy could be reduced by 86.1 percent in the skin test-negative group and 70.0 percent in the skin test-positive group, relative to strict avoidance of peanut. This study, however, has a number of limitations with regard to clinical practice that need to be carefully understood:
- The participants in this study were of a narrow age-range and were carefully selected with regard to risk factors for allergy. The results of this study are not clearly generalizable to other groups, such as infants of other ages, infants with other baseline food allergies than egg, infants with mild eczema, infants with asthma, or any other presentation different from the group that was carefully selected for this study.
- The participants in this study had a high rate of adherence to the study protocol. In the real world, many families may not be so rigorous in giving large doses of peanut at least three times a week until age 60 months.
- It is unknown what would happen in these children after age 60 months. The investigators, in fact, stated in their manuscript that they will be tracking the future progress of the participants in the study.
- This study was specifically for peanut allergy. It is not possible to generalize these results to other food allergies, since different food allergies do “behave” differently.
- The rate of peanut allergy was not zero in any of the groups studied. This study showed amazing promise to a population of high-risk infants, but some of these infants still developed peanut allergy.
- The researchers were careful and rigorous in the performance of their study, but nine children, at the end of the trial, did need injectable epinephrine after their oral challenges to peanut. In other words, even in a highly-controlled research setting, some study participants had dangerous symptoms.
Therefore, this study should be viewed with excitement and hope since it significantly advances our understanding of the prevention of peanut allergy. It may not, however, signify a large change to current practice since the study population was narrowly selected, and there is some real risk for harm. Finally, the information from this trial should not be used to attempt to prevent or treat peanut allergy (or any other food allergy) at home. A board-certified allergist-immunologist is the best resource for advice about the prevention, evaluation, and management of peanut allergy.
Brian Smart is an allergy-immunology physician who blogs at An Allergist/Immunologist’s Guide to Living Well.