FOOD ALLERGY IN CHILDREN

Food allergy - General aspects of food allergy diagnosis and management
Food allergy is frequently encountered in general pediatric practice. The prevalence of food allergy in children appears to be increasing for reasons that are still poorly understood. The most important aspect of the care of these children is to know the clinical features of food allergy and to recognize the limitations of the currently available tests for food allergy, to prevent unnecessary dietary limitations and anxiety. A recent review and journal supplement summarize clinical features of these often confusing disorders.

Important points regarding IgE-mediated food reactions are that the levels of food-specific IgE predictive of clinical reactivity vary by food and age and the level of food-specific IgE is not necessarily predictive of the severity of reaction. Also, as demonstrated in a recent study of carefully conducted food challenges, the natur of the original reaction should not be assumed to be predictive of the nature of future reactions. Subsequent reactions can be more severe and involve different organ systems. Referral to a board-certified pediatric allergist should be considered for evaluation of these patients for food-specific IgE and closely observed oral food challenges when indicated. In addition, children with multiple food allergies may benefit from consultation with a nutritionist familiar with the management of food allergy and from food allergy support groups.

Prevalence of peanut allergy among children rising
Peanut and tree nut allergy are particularly severe and persistent food allergies. Two recent studies sought to determine the prevalence of peanut and/or tree nut allergy among children. One of the studies was a followup, random digit dial telephone survey from a study reported in 1997, which reported 0.4% of children under the age of 18 years with peanut allergy and 0.2% with tree nut allergy. The follow-up survey was conducted in 2002 to determine if the prevalence among children has changed over time. Based on 4855 households participating in the survey, representing 13,493 individuals in the US, the overall rate of peanut and tree nut allergy was not significantly changed over 5 years, but the rate of reported peanut allergy among children doubled to 0.8%. This increase in prevalence among children is consistent with a study reported from the United Kingdom. A Canadian cross-sectional study evaluating children in kindergarten to grade 3 in school classrooms, used questionnaires, testing for peanut-specific IgE, and oral peanut challenges. Using conservative assumptions, 1.34% of children were identified as peanut allergic. Clearly the prevalence of peanut allergy is increasing among children and more effective methods for evaluation and management must be developed.

Natural history of peanut allergy
Recent studies have demonstrated that up to 20% of peanut allergic patients will lose the allergy over time. A more recent study correlating CAP-RAST measurements of peanut-specific IgE levels with oral food challenge results demonstrated that, among children under 5 years of age who had peanut-specific IgE levels < 5kU/L by CAP-RAST testing, around 50% outgrew their peanut allergy. Recurrence of peanut allergy was reported in two patients after successful completion of an oral challenge, although only one was confirmed. Similar recurrences have been reported previously. Careful follow-up, with determination of peanutspecific IgE levels and oral food challenges when appropriate, is required to ensure that children are not unnecessarily labeled as peanut allergic.

Environmental exposures to food allergens
Allergen avoidance is the only method currently available for preventing food reactions. Several reports have suggested that accidental exposure to food allergens through the skin or by inhalation have led to reactions [46–48], although typically, ingestion is not excluded in these reports. Food reactions occurring in school have been reported in 18% of food-allergic children participating in a telephone survey [49]; peanut or tree nut reactions occurring in school have been reported in 16% of children participating in the US Peanut and Tree Nut Allergy Registry [50]. These reports have understandably led to great anxiety as food-allergic children attend daycare centers and schools where peanut allergen may be present, most typically in the form of peanut butter. To address this concern, two recent reports have carefully evaluated the risk of reactions from casual contact with peanut butter and the distribution of peanut allergens in schools and other environments. In the first study, 30 children highly sensitive to peanut were exposed cutaneously to peanut allergen, by application of peanut butter to the skin for 1 minute, or by inhalation, by having subjects breathe 12 inches from a standardized surface area of peanut butter for 10 minutes. Cutaneous application of peanut butter led to cutaneous reactions in 33% of the patients in the study, which is not unexpected. Exposure to the skin or inhalation, however, did not induce systemic or respiratory reactions in any of the patients in the study. As noted by the authors, the results apply only to peanut butter and should not be generalized to exposure from roasted peanuts or other forms. The second study measured levels of the major peanut allergen, Ara h 1, in simulated environments and in schools and preschools. Following the application of a large amount of peanut butter to tables or hands, cleaning with standard cleaning agents led to undetectable Ara h1 levels on the surfaces (lower limit of detection 30 ng/milliliter). The only exceptions were that with washing tables with dish soap or washing hands with plain water alone or with antibacterial hand sanitizer, residual allergen was detected, although at significantly reduced levels. Samples taken from 6 preschools and schools of table surfaces, food preparation areas, water faucets, and desks demonstrated detectable Ara h1 on only 1 of 71 surfaces sampled. These studies are reassuring; however, continued vigilance must be exercised to ensure careful cleaning of tables, hands, and other potentially contaminated surfaces and, most importantly, to prevent accidental ingestion of foods containing food allergens. Training school personnel on the importance of food allergen avoidance and on the signs of food reactions and proper administration of epinephrine are critical areas to be addressed to increase school safety.


Provision of self-injectable epinephrine to children with food allergy
In addition to education on food allergen avoidance, all patients with food allergy at risk for anaphylaxis should be prescribed self-injectable epinephrine devices, instructed on proper administration, and given action plans that include calling for emergency transport after administration of epinephrine. Approximately 30,000 anaphylactic reactions to food are estimated to occur in the US yearly with 150 deaths. Reviews of fatal anaphylactic reactions to foods demonstrate that either delay or failure to administer epinephrine is common in fatal food anaphylaxis. In one study analyzing 32 fatalities reported to a national registry, only 10% of the subjects had epinephrine available at the time of the reaction, although all but one had known food allergy with prior reactions. Among the fatalities in the registry with sufficient data, most were among adolescents and young adults, all but one had asthma, and peanut and tree nut were the most common cause. A recent review highlights many of the issues regarding administration of epinephrine for anaphylaxis in children, including choosing the appropriate dose.

Emergency department management of food anaphylaxis
While guidelines on the importance of prompt epinephrine administration to reverse anaphylactic reactions have been developed, a recent report demonstrates that emergency department management of anaphylaxis may be suboptimal. As part of the Multicenter Airway Research Collaboration, charts of patients presenting with food allergy in 21 emergency departments were reviewed. Among the patients in the cohort with severe anaphylactic reactions, only 24% received epinephrine. Although less than 50% of the patients were diagnosed with the food allergy prior to presenting with the reaction, only 16% were prescribed self-injectable epinephrine and 12% were referred to an allergist at the time of discharge. While it is difficult to determine the reasons for not administering epinephrine from an emergency department chart review, great effort must be made to ensure that all caregivers are familiar with guidelines for the treatment of anaphylaxis and that patients are discharged with self-injectable epinephrine and instructions for allergen avoidance and follow-up.

Posture and outcome of anaphylaxis
The posture of patients having anaphylactic reactions may be important in determining outcome of anaphylactic reactions, as suggested in a recent letter by an expert in the area of fatal anaphylaxis. In a review of 214 fatal anaphylactic reactions since 1992, a pattern was noticed among cases of anaphylactic shock occurring outside of the hospital that several deaths occurred soon after the patients assumed a more upright posture. In several of the cases with sufficient data, death occurred within seconds of either sitting or standing. Based on these findings, it is proposed that patients experiencing anaphylactic reactions leading to collapse or those feeling faint from impending shock should be kept in a supine position, including during self-administration of epinephrine. Exceptions are patients with respiratory distress or vomiting. Although not part of the advanced life support guidelines, it is important to be aware of these observations.

Anti-IgE treatment for peanut allergy
Interventions to reduce the risk of anaphylaxis from exposure to food allergens are needed. In a large, carefully designed, randomized, double-blind, placebo-controlled study, anti-IgE antibody (TNX-901, Tanox, Inc., USA) was administered subcutaneously every 4 weeks for 4 doses to patients with peanut hypersensitivity. Administration of anti-IgE reduced the serum levels of total IgE and raised the threshold dose for reaction in a dosedependent manner. This response may be beneficial to prevent reactions from accidental exposures, but the level of elevation of threshold of reactivity is variable and unpredictable, depends on regular, long-term administration, and does not reverse the underlying immune dysfunction. In addition, the antibody (TNX-901) used in the study is not currently available and Xolair (Genentech and Novartis, USA), which is approved for use in a subset of patients with asthma, has not been studied for similar benefits.

Food allergy conclusion
Current research is focused on identifying diseasemodifying therapies to reverse the underlying immune dysfunction leading to IgE-mediated food allergy. Until such disease-modifying treatments are available, strict avoidance of food allergens and readily available access to self-injectable epinephrine remain the mainstays of treatment. Families of food allergic children must be educated regarding recognition of anaphylactic reactions, proper administration of epinephrine, foods and ingredients to be avoided. Given the complexity of the diagnosis, evaluation, and treatment of these patients, referral to a board-certified allergist with expertise in food allergy should be considered. Multidisciplinary approaches should be considered for these patients to ensure optimal care.