Food Allergy Testing in the Coming Age of Prescription Immunotherapy

By Andrew Bird, MD

Shortly after finishing fellowship training I saw a patient who shaped my thinking and my practice ever since.

Angela was a 15 month-old little girl who came to the Children’s emergency room with her skin peeling off and swelling of her arms, legs, hands and feet. Her primary care physician felt that her eczema had significantly worsened and sent her to the hospital for further evaluation. After a few basic labs, it became apparent the child was significantly malnourished. Her rash was not due to eczema, but rather it was a result of severe zinc deficiency. The swelling was due to inadequate protein in her diet. Further questioning revealed that the child’s mother believed the child had multiple food allergies and inadequate evaluation led her primary physicians to believe this to be true. Thankfully this story has a happy ending. The child received proper nutrition in the hospital and food challenges revealed that she was not allergic to any foods.

This case was published in the premier pediatrics journal (Alvares M, et al. Pediatrics 2013; 132;e229) to broaden our message to Pediatricians who often see these patients on the front lines.

Angela in particular brought new focus to the long list of patients referred to my clinic to unravel whether or not they have food allergies. Several times a day I examine patients—mostly children–diagnosed with numerous food allergies based on a test, and then after taking a thorough diet history it often becomes apparent they are not allergic to any foods. Severe malnutrition is the most immediate consequence of misdiagnosis. The long-term consequence, as any food allergy family will tell you, is the hardship of avoidance, fear, and the logistics of shaping the patient’s environment at home and at school.

This experience motivated me to review the charts of patients referred to my practice over approximately a 1-year period. Out of the 797 new patients I evaluated in that time period 35% of the patients had received specific IgE testing to a standard “panel” of food allergens.

The presence of specific IgE to a number of foods may or may not be pertinent to the individual’s health. We found that after taking a thorough diet history many of the tests were irrelevant because the children were often eating the foods without having an immediate reaction. Tests had been ordered for a number of reasons that had nothing to do with immediate reactions to foods, including allergic rhinitis symptoms, stomach pain, and rashes of uncertain etiology.

In our practice we did additional evaluation including skin tests and food challenges when warranted and were able to re-introduce at least 1 food into the diets of 89% of the kids. They were avoiding a food unnecessarily. On average, children who were being evaluated were avoiding more than 4 foods, and after evaluation an average of 2 foods per child were reintroduced. (Bird JA, et al. J Pediatrics 2015;166:97-100)

Our group is not the first to report misdiagnosis with inappropriate application of food allergen panel testing. David Fleischer and colleagues at National Jewish Health looked at 125 children being evaluated for food allergy (Fleischer DM, et al. J Pediatrics 2011;158:578-83). After performing oral food challenges they were able to reintroduce 84-93% of avoided foods, and they concluded that reliance on serum food-specific IgE testing for food allergy diagnosis is especially poor in children with atopic dermatitis.

The Advent of Prescription Immunotherapy

This message has new urgency as we now move into an era of food allergy therapeutics. The burden of misdiagnosis has been borne by patients and their families in the form of anxiety, life-style alteration, and expensive yearly purchase of emergency medicine. As experimental therapies come on the market some of costs will be carried by health insurance companies as well as family health-care budgets.

This new welcome development will also present new challenges to food allergy diagnostics. At the present time the standard treatment for life-threatening food allergies is to avoid the allergen, but once treatment options are readily available the question surfaces whether or not patients will be appropriately diagnosed before embarking on a treatment course. Once a therapy is available it seems likely that many patients will be funneled directly to treatment with even less emphasis on the oral food challenge to ensure accurate diagnosis before committing to years of treatment.

The response from the medical community must be to ensure that patients are appropriately diagnosed and diagnostic methods are used intentionally in patients with a history supporting a role of immediate reactivity following food ingestion. Ongoing research into food allergy diagnostics is uncovering a role for more precise testing methods with modalities such as basophil activation testing or, in some cases, the utilization of component resolved diagnostic IgE tests and various complicated algorithms.

For now, the superior test for diagnosis of food allergy remains the oral food challenge conducted in the office of a specialist equipped for treating a reaction should one occur and with the expertise to identify the reaction early during the challenge. Until better testing methodologies become commercially available, we must rely on these challenges to properly diagnose our patients, and we must consider this option with even greater enthusiasm before committing them to years of therapy.

Dr. Andrew Bird is a Dedman Family Scholar in Clinical Care, the director of the Food Allergy Center at Children’s Medical Center Dallas, and assistant professor of pediatrics and internal medicine in the Division of Allergy and Immunology at UT Southwestern Medical Center. He is currently working with colleagues in several ongoing clinical trials using food proteins for immunotherapy.