Food allergy is an important public health problem because it affects children and adults, it may be severe and even life-threatening, and it may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases (NIAID), working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. These guidelines, which were published in 2010, did not offer strategies for the prevention of food allergy due to a lack of definitive studies at the time.1
In February 2015, the New England Journal of Medicine published the results of the Learning Early about Peanut Allergy (LEAP) trial.2 This landmark clinical trial showed that introduction of peanut products into the diets of infants at high risk of developing peanut allergy was safe and led to an 81% relative reduction in the subsequent development of peanut allergy. The LEAP trial results, combined with other emerging data, strongly suggested that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. This growing body of evidence raised the need for clinical recommendations focusing on peanut allergy prevention.
To achieve this goal and its wide implementation, NIAID invited the members of the 2010 guidelines coordinating committee and other stakeholder organizations to develop this addendum on peanut allergy prevention to the 2010 Guidelines for the Diagnosis and Management of Food Allergy in the United States.
DEVELOPMENT OF THE 2017 ADDENDUM
The NIAID established a coordinating committee (Table 1) to oversee the development of the addendum; review drafts of the addendum for accuracy, practicality, clarity, and broad utility of the recommendations in clinical practice; review and approve the final addendum; and disseminate the addendum. The committee members represented 26 professional organizations, advocacy groups, and federal agencies.
In June 2015, the coordinating committee convened an expert panel chaired by Joshua Boyce, MD. The 26 panel members, listed in Table 2, were specialists from a variety of relevant clinical, scientific, and public health areas. Panel members were nominated by the coordinating committee organizations, and the composition of the panel received unanimous approval by these member organizations.
The charge to the expert panel was to use the literature review prepared by the NIAID, in conjunction with consensus expert opinion and expert panel-identified supplementary documents, to develop evidence-based recommendations for the early introduction of dietary peanut to prevent peanut allergy. The new guidelines are intended to supplement and modify Guidelines 37 to 40 in Section 5.3.4 of the 2010 Guidelines: Prevention of Food Allergy.1
NIAID staff conducted a literature search of PubMed, limited to the years 2010 (January) to 2016 (June). Sixty-four publications (original research articles, editorials/letters, and systematic reviews) were deemed relevant and placed into two tiers: tier 1 contained 18 items, considered highly relevant to the early introduction of peanut or other allergenic foods; and tier 2 contained 46 items on related topics such as food allergy or eczema prevention.
Assessing the quality of the body of evidence
For the tier 1 references, the expert panel assessed the quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Preparation of the addendum
Draft versions of the addendum were reviewed by the coordinating committee members, open to public comment, revised accordingly, and approved by the expert panel and the coordinating committee.
DEFINING THE STRENGTH OF EACH CLINICAL GUIDELINE
The expert panel has used the verb recommends or suggests for each clinical recommendation. These words convey the strength of the recommendation, defined as follows:
- Recommend is used when the expert panel strongly recommended for or against a particular course of action.
- Suggest is used when the expert panel weakly recommended for or against a particular course of action.
The expert panel came to consensus on the following three definitions used throughout the addendum guidelines.
- Severe eczema is defined as persistent or frequently recurring eczema with typical morphology and distribution assessed as severe by a healthcare provider and requiring frequent need for prescription-strength topical corticosteroids, calcineurin inhibitors, or other anti-inflammatory agents despite appropriate use of emollients.
- Egg allergy is defined as a history of an allergic reaction to egg and a skin-prick test wheal diameter of 3 mm or greater with egg white extract, or a positive oral egg food challenge result.
- A specialist is defined as a healthcare provider with the training and experience to perform and interpret skin-prick tests and oral food challenges and know and manage their risks. Such persons must have appropriate medications and equipment on site.
The addendum guidelines are summarized in Table 3.
Addendum guideline 1
The expert panel recommends that infants with severe eczema, egg allergy, or both have introduction of age-appropriate peanut-containing food as early as age 4 to 6 months to reduce the risk of peanut allergy. Other solid foods should be introduced before peanut-containing foods to show that the infant is developmentally ready. The expert panel recommends that evaluation with peanut-specific IgE (peanut sIgE) measurement, skin-prick tests (Table 4), or both be strongly considered before introduction of peanut to determine if peanut should be introduced and, if so, the preferred method of introduction (Figure 1). To minimize a delay in peanut introduction for children who may test negative, testing for peanut sIgE may be the preferred initial approach in certain healthcare settings, such as family medicine, pediatrics, or dermatology practices, in which skin-prick testing is not routine. Alternatively, referral for assessment by a specialist may be an option if desired by the healthcare provider and when available in a timely manner.
If the decision is made to introduce dietary peanut based on the recommendations of addendum guideline 1, the total amount of peanut protein to be regularly consumed per week should be 6 to 7 g over three or more feedings.
Quality of evidence: Moderate. The designation of the quality of evidence as “moderate” (as opposed to “high”) is based on the fact that this recommendation derives primarily from a single randomized, open-label study: the LEAP trial. However, it should be noted that the assessment of the LEAP trial's primary outcome was based on a double-blind, placebo-controlled oral food challenge. Furthermore, confidence in this recommendation is bolstered by the large effect size demonstrated in the LEAP trial and prior epidemiological data that peanut allergy is relatively infrequent in Israel, where early childhood consumption of peanut is common.
Contribution of expert opinion: Significant.
Breastfeeding recommendations: The expert panel recognizes that early introduction of peanut may seem to depart from recommendations for exclusive breastfeeding through age 6 months. However, it should be noted that data from the nutrition analysis of the LEAP cohort indicate that introduction of peanut did not affect the duration or frequency of breastfeeding, and did not influence growth or nutrition.
Age of peanut introduction: For children with severe eczema, egg allergy, or both, the expert panel recommends that introduction of solid foods begins at ages 4 to 6 months, starting with solid food other than peanut. However, it is important to note that the infants in the LEAP trial were enrolled between ages 4 and 11 months and benefitted from peanut consumption regardless of age at entry. Therefore, if the 4- to 6-month time window is missed for any reason, including developmental delay, infants may still benefit from early peanut introduction.
Considerations for family members with established peanut allergy: The expert panel recognizes that many infants eligible for early peanut introduction under this guideline will have older siblings or caregivers with established peanut allergy. The expert panel recommends that in this situation caregivers discuss with their healthcare providers the overall benefit (reduced risk of peanut allergy in the infant) versus risks (potential for further sensitization and accidental exposure of the family member to peanut) of adding peanut to the infant's diet.
Children identified as allergic to peanut: For children who have been identified as allergic to peanut, the expert panel recommends strict peanut avoidance. This may include those children who fail the supervised peanut feeding or the oral food challenge, or those children who, upon further evaluation by a specialist, are confirmed as being allergic to peanut. These children should be under long-term management by a specialist.
Addendum guideline 2
The expert panel suggests that infants with mild-to-moderate eczema should have introduction of age-appropriate peanut-containing food around age 6 months, in accordance with family preferences and cultural practices, to reduce the risk of peanut allergy. Other solid foods should be introduced before peanut-containing foods to show that the infant is developmentally ready. The expert panel recommends that infants in this category may have dietary peanut introduced at home without an in-office evaluation. However, the expert panel recognizes that some caregivers and healthcare providers may desire an in-office supervised feeding, evaluation, or both.
Quality of evidence: Low. The quality of evidence is low because this recommendation is based on extrapolation of data from a single study.
Contribution of expert opinion: Significant.
Addendum guideline 3
The expert panel suggests that infants without eczema or any food allergy have age-appropriate peanut-containing foods freely introduced in the diet together with other solid foods and in accordance with family preferences and cultural practices.
Quality of evidence: Low.
Contribution of expert opinion: Significant.
1. Boyce JA, Assa'ad A, Burks AW, et al Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol
. 2010;126(6 suppl):S1–S58.
Copyright © 2017 American Academy of Physician Assistants
2. Du Toit G, Roberts G, Sayre PH, et al Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med