What Is Food Allergy
A food allergy is defined as "a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to given food." Various symptoms of food allergy occur in many organs. Food allergies are classified roughly into 4 clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type food allergy (urticaria, anaphylaxis, etc.), and (4) food dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate food allergy).
The therapy for food allergies includes treatment of and prophylactic measures against hypersensitivity such as anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be used only if necessary because of the patient-related burden. For this purpose, it is very important that causative foods be accurately identified.
There are a number of means available to identify causative foods, including the history taking, a skin prick test, detection of antigen-specific IgE antibodies in the blood, the basophil histamine release test, the elimination diet test, and the oral challenge test, etc. Of these, the oral challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions, such as anaphylaxis.
ELISA For Food Allergy
Food allergy testing by IgG ELISA/EIA panels is a convenient and easy way to diagnose food allergies in a patient. It is, however, a testing method that is questionable in both its theory and validity. It is also costly and may not be reliable, depending on which laboratory you use.
Food Allergy Treatment
The possibility of severe fatal reactions with accidental ingestions and lack of standard treatment has led to a strong push to find a viable therapy option for patients. Therapy can be separated into allergen-specific and allergen non-specific immunotherapy. Several small studies have previously been published and now larger, multi-center trials are underway. However, caution must be used when interpreting study results as there is a difference in the outcomes of desensitization and tolerance. Desensitization is a change in the threshold or amount of the allergen needed to induce a reaction whereas tolerance is achieved when one can ingest the allergen on an ad lib basis without reaction. Tolerance is a long lasting immunity while with desensitization one must continue to ingest the allergen daily or the immunologic changes may be lost. Induction of tolerance would be considered curative for the food allergy.
Allergen specific therapies include oral immunotherapy (OIT), sublingual immunotherapy (SLIT) and epicutaneous immunotherapy (EPIT). OIT involves introducing the food allergen in initial quite low oral doses, and typically escalating the dose over a day or two of rapid dose increase, followed by a slower incremental dose increase over weeks and months. Varying OIT protocols have been used in several small trials showing promise for desensitization to food allergens .
A multi-center double-blind, randomized, placebo controlled study of OIT in egg allergic children showed both safety and efficacy with a desensitization rate of 75 per cent in the OIT receiving subjects after 22 months of therapy . Peanut OIT has been a particular focus given that peanut is a major cause of food-induced anaphylaxis. However, a recent Cochrane review of peanut OIT trials found only one randomized control trial that resulted in desensitization, yet with a risk of clinically-significant adverse reactions .
Though many adverse events have been noted in the studies, especially in the more rapid dose escalation phases, no life threatening event or death has been reported thus far . However, a proportion of patients (~10-20%) in each study appear to be unable to tolerate desensitization due to the side effects of therapy . The Cochrane review authors note that due to the risk of adverse events and current lack of evidence of long-term benefits, peanut OIT cannot currently be recommended without further study.
An alternative form of oral therapy exists for cow milk and egg allergy. Subsets of children who are reactive to unheated or lightly cooked egg and milk have been noted to have tolerance of items containing these allergens that are extensively heated. The food protein is thought to be denaturated, with the heat labile protein undergoing a conformational change secondary to the high heat of cooking rendering it to be non allergenic to some patients. Studies have shown that introduction of extensively heated milk and egg appears to hasten the development of tolerance to the unheated food protein . Introduction of extensively heated egg and milk in tolerant children may have immunomodulatory benefit and may potentially be safe in inducing tolerance in the traditional OIT .
Similar to OIT, SLIT uses small escalating doses of the food allergen; however, doses are given under the tongue via an extract vehicle. Studies have shown SLIT thus far to be quite safe , yet concerns for its efficacy exist as SLIT is unable to achieve the high doses that appear to be necessary in OIT to induce desensitization. The first multi-center, randomized, placebo-controlled study of peanut SLIT showed a modest desensitization at OFC after 44 wk of therapy with 14 of 20 subjects receiving peanut SLIT being able to consume at least a 10-fold increase in the amount of peanut powder they were able to consume when compared to their baseline OFC .
The majority of adverse reactions to doses involved the oral-pharyngeal mucosa with only one subject receiving epinephrine at home for oral-pharyngeal symptoms that progressed to cough after antihistamine dosing . In a direct comparison study of SLIT versus OIT for cow milk allergy, systemic reactions were more common with OIT, however, OIT was more efficacious than SLIT alone . However, SLIT remains an appealing therapy to study given it is less likely to cause serious adverse reactions.
Fewer trials so far, have evaluated the administration of allergen via the skin in a patch form in EPIT. In a pilot study using EPIT for the treatment of cow milk allergy, a trend to improvement was noted, but there was no significant increase in the cumulative total dose of cow milk tolerated after three months of therapy with only local reactions being noted. Peanut EPIT has shown promise in mice models of allergy . A Phase Ib trial of peanut EPIT in humans showed mostly local, cutaneous adverse events with no significant difference in systemic reactions between the EPIT and placebo groups .
Therapies for food allergy in general that are not directed to a specific allergen are also in the midst of study. The food allergy herbal formula-2 (FAHF-2) is a capsule containing a Chinese herbal formula found to abolish anaphylaxis in mice with peanut allergy . Subsequent extended phase I trials in humans showed dosing of the nine herb formula to be both safe and well tolerated over a 6 month period .
The monoclonal anti-IgE antibody omalizumab has also been found to be a potential non-specific allergen therapy. A multi-center, randomized, double-blind, placebo-controlled phase II trial using omalizumab in the treatment of peanut allergy completed 14 of the planned 150 subjects prior to early discontinuation due to severe anaphylactic reactions during the qualifying OFCs .
Of the 14 completing the study, subjects receiving omalizumab trended in tolerating an increased amount of peanut protein following the 24 wk of therapy when compared to placebo . While the data are limited on using omalizumab as a single agent for the treatment of food allergy, focus has shifted to study if omalizumab has a role in OIT, as an adjunct to limit side effects seen in OIT dose escalation. A pilot study using omalizumab as an adjunct to cow milk OIT demonstrated that omalizumab permitted rapid milk dose escalation in a majority of subjects . Multiple centers have elected to study this further.