Food-Specific and Component IgE Threshold Levels That Predict Food Allergy in People With Elevated Total Serum IgE Levels and Atopic Dermatitis

Allergy skin prick tests and measurement of food-specific immunoglobulin E (IgE) levels are common but not robust means to diagnose food allergy, so patients may be placed on overly restrictive food elimination diets as a result of false-positive results. Such restrictions can lead to poor weight gain, malnutrition, and negative impact on quality of life. More than half of patients who are sensitized (ie, have a positive IgE test) to a particular food do not react to it during an oral food challenge, the gold standard for diagnosing food allergy. Development of food allergy does not always correlate to food-specific IgE levels. The care of these patients would be dramatically improved if decision points for food-specific or component IgEs could be identified that predict when an immediate hypersensitivity is present. This is especially an issue among patients with atopic dermatitis (AD), the most common chronic, relapsing inflammatory disorder of the skin affecting children. Patients with AD are more likely to develop other allergic conditions, including food allergy and sensitization. AD patients are also likely to have high levels of total serum IgE.

In this study, participants aged 3-21 years (n = 175) with elevated total serum IgE levels and a history of AD will undergo open feedings and/or double-blind, placebo-controlled food challenges (DBPCFCs). Open feedings will be 1- or 2-step, depending on how often the participant regularly consumes the food at home. There are two DBPCFCs to milk: milk powder or placebo baked into a muffin, and straight milk powder or placebo mixed with a vehicle. The DBPCFC for peanut will be done with peanut flour or placebo mixed with a vehicle. Blood will be collected during the study for measurement of total and component IgEs as well as potential biomarkers of food sensitization vs. immediate hypersensitivity and reaction severity. From these data, we hope to identify diagnostic IgE threshold levels that will inform when oral food challenges are warranted in patients with elevated total serum IgE levels and AD, which is critically needed in the allergy field to facilitate the care of these patients.

• INCLUSION CRITERIA:

Individuals must meet all of the following criteria to be eligible for study participation:

• Aged 3-21 years.
• Currently enrolled on study 15-I-0162, "Natural History and Genetics of Food Allergy and Related Conditions."
• Has a total serum IgE level >= 900 kU/L at time of screening.
• Has a history of AD based on self-report or physician assessment.
• Willing to undergo an oral food challenge to both placebo and test food.
• Willing to allow storage of blood samples for future use in medical research.
• Willing to allow genetic testing to be conducted on blood samples.
• Has a primary care physician or other physician who will manage all health conditions related or unrelated to the study objectives.
• Be willing to discontinue omalizumab or dupilumab within 6 months of a food challenge,and antihistamines and oral steroids prior to a food challenge, as these drugs might interfere with the oral food challenge procedure. Use of topical steroids will be allowed
• Able to provide informed consent.

EXCLUSION CRITIERIA:

Individuals meeting any of the following criteria will be excluded from study participation:

• Pregnant.
• Known genetic disorder that causes an elevation in total IgE level or one that could affect the severity of an anaphylactic response.
• Known cardiac disease.
• Current use of a beta-blocker.
• Active eosinophilic gastrointestinal (GI) disorder including eosinophilic esophagitis, currently symptomatic, unless they are currently on treatment and have had a negative esophageal biopsy via endoscopy within at least the past 18 months, and/or unless the study food is already in the participants diets.
• Any chronic medical condition requiring long-term use of oral steroids.
• Current or recent (within previous 6 months) use of omalizumab or dupilumab.
• Any condition that, in the opinion of the investigator, contraindicates participation in this study.

Co-enrollment guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies. Consideration for co-enrollment in trials evaluating the use of a licensed medication will require the approval of the principal investigator. Study staff should be notified of co-enrollment on any other protocol as it may require the approval of the principal investigator.