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New Research Fuels Growth in Food Allergy

Basic science research has greatly increased the understanding of food allergy in recent years, and that has fueled promising advances in diagnostic testing of allergen components. Three speakers reviewed this research and the development of management strategies September 21 during the Miniseminar “Food Allergy 2016: The State of the Science.”

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Karen Calhoun, MD, reviews the state of knowledge of food allergy.

Food allergy is increasing, with 5 percent to 8 percent of infants and 3 percent to 5 percent of adults diagnosed with allergies. In addition, 25 percent of people think they have allergies, said speaker Karen Calhoun, MD, who reviewed the state of knowledge of food allergy. She is a professor in the Department of Otolaryngology-Head and Neck Surgery at The Ohio State University Wexner School of Medicine.

Eight foods cause 90 percent of food allergies—tree nuts, egg, milk, peanut, soy, shellfish, fish, and wheat. Family history is a strong indicator of susceptibility to atopic disease. Research shows that most children outgrow allergies as the gut and immune system mature, she said.

Complicating diagnosis is the confusion of food allergy with food sensitivity. Those with food sensitivity can test positive for allergens but can tolerate the food without problems, and they should continue eating those foods regularly, Dr. Calhoun said.

Theoretically, we should all be allergic to food because the role of the human immune system is to detect and destroy foreign material, including food. The immune system overcomes this through oral tolerance, which is the state of local and systemic immune unresponsiveness. Problems with the oral tolerance process lead to autoimmune diseases and food allergies, she said. The dynamic tolerance theory says that early exposure to high doses of an allergen can cause oral tolerance, as do persistent, low doses of an allergen. In-between doses stimulate immunologic responses.

Another theory about the development of food allergies is the hygiene hypothesis, which is expanding into the dual allergen hypotheses, Dr. Calhoun said. That theory says that sensitization occurs via the skin and gastrointestinal tract, with transcutaneous food protein exposure leading to a Th2 response and gut exposure to food protein leading to a Th1 response. Food allergy or tolerance depends on the balance and timing of the exposures.

It also is known that the gut microbiome can be allergy-protective or make a patient more likely to develop allergies, Dr. Calhoun said. Microbial colonization begins with the passage through the vaginal canal at birth, or earlier, and that affects both the innate and adaptive immune systems. Disrupting intestinal microflora results in side effects such as diarrhea or yeast infections that are treated with antibiotics. That changes the priobiotic population and can permanently alter its composition.

“It appears that multiple courses of antibiotics can predispose to food allergies,” Dr. Calhoun said. “Encouraging rich diversity of the gut microbiome is associated with fewer atopic diseases.”

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Cecelia Damask, DO, discusses a new form of testing—component-resolved diagnostic (CRD) testing.

Scientific advances also are driving change in food allergy diagnostic testing, said Cecelia Damask, DO, who focuses on allergic disorders in her practice in Lake Mary, FL. Testing research has found that sensitization is the presence of allergen-specific IgE in vitro or in vivo and does not necessarily indicate allergy.

A large portion of peanut-sensitized individuals are not actually allergic, she said. Not all individuals ordering allergy tests understand their limitations and not enough challenges are being done to determine the validity of a diagnosis. National Institutes of Health guidelines highlight the difference between sensitivity and allergy, adding that diagnostic tests cannot be the only means of diagnosing food allergy.

Tests for allergy include skin prick and serum testing, both of which are imperfect, with high sensitivity and poor specificity, Dr. Damask said. Those tests should focus on foods suspected of provoking the reaction.

An advanced form of food allergy testing being used in Europe is component-resolved diagnostic (CRD) testing. The idea of CRD is that foods often have more than one protein that individuals can be allergic to. For example, Ara h1, h2, and h3 are peanut proteins most correlated to severe allergic reactions in individuals with a peanut allergy. The other peanut proteins can give a positive allergy result on a test but only cause mild reactions.

CRD testing seeks to discriminate between sensitization to stable (dangerous) or labile (most not dangerous) allergens present in the same food source and to predict possible cross-reactivity to other food sources containing homologous allergens, Dr. Damask said. This could clarify cross-reactivity versus primary sensitization with clinical relevance, and predict the response to therapy/challenge and ideal therapy candidates.

A study in the United Kingdom tried to determine reactions to protein peanuts and found that ARA h2 provided the best positive predictive value. The data is promising, but limited, and is not ready for clinical use yet, she said. The limitations of CRD are that no single component has absolute diagnostic value and clinical correlation is still necessary in diagnosing food allergy.

William Reisacher, MD, presents an update on the management of food allergy.

William Reisacher, MD, presents an update on the management of food allergy.

The session’s final presentation, by William Reisacher, MD, focused on the management of food allergy. He is an associate professor in the Otolaryngology-Head and Neck Surgery Department at Weill Cornell Medical College, New York, NY. He presented updates on prevention, avoidance, medical therapies, desensitization, and achieving oral tolerance.

In the area of prevention, studies of maternal diet, hydrolyzed formulas, and the protective effect of breastfeeding on the development of atopic dermatitis in children are inconclusive, he said.

Avoidance uses elimination for IgE-mediated food allergy, as well as diets to manage atopic dermatitis. Studies have found the approach helpful, Dr. Reisacher said. Labeling of food ingredients still is not clear and accidental exposures occurred in 58 percent of food allergy patients during a five-year period, and 75 percent of patients over 10 years.

Medical therapies discussed focused on the effectiveness of epinephrine, dietary patterns and supplements, and biologics. Epinephrine auto-injectors help, but need to be carried by more patients. For diets, probiotics may be helpful for atopic dermatitis, but the data is not conclusive, and the data is conflicting on the use of antioxidants, folates, and vitamin D. In the area of biologics, omalizumab has been found to increase the threshold to reaction for peanut.

For desensitization, subcutaneous immunotherapy and sublingual immunotherapy had mixed results. Oral immunotherapy led to successful desensitization, but safety and tolerability limits it use. Epicutaneous immunotherapy has been shown to be effective for food allergy in animal models and for airborne allergy in humans, and studies are now ongoing.

Future directions being studied are peptide immunotherapy, recombinant allergens, immunostimulatory adjuvants, and other allergen modifications.

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