A 2-year-old with Hives and Lip Swelling
After reading this article and answering the review questions, the reader will be able to:
- Recognize the various presentations of IgE-mediated food allergy
- Diagnose food allergy, specifically peanut allergy
- Describe the protocol for treating food-induced anaphylaxis
An otherwise healthy 2-year-old boy presents to your office after developing a red rash with small raised “white bumps” all over his body and a cough at daycare. In your office, he then begins to drool and lip swelling is noted. Symptoms began immediately after drinking milk and eating a peanut butter cookie during snack time. His parents had previously avoided peanuts in his diet because of their concern about a possible peanut allergy.
Figure: Urticarial rash developed after eating peanuts
Clinical Manifestations of Food Allergy
Food allergy is defined as an adverse reaction to a food due to an immunologic mechanism. In IgE-mediated reactions, clinical manifestations most commonly involve the skin, gastrointestinal tract, and respiratory tract in that order. Clinical symptoms can develop within seconds or more slowly, but usually occur within two hours after ingestion. In about one-third of severe reactions, a biphasic, or secondary late-phase allergic response can occur up to four hours later. Asthma is an important risk factor for more severe reactions.
Food allergy can produce local reactions or systemic symptoms, such as anaphylaxis. In July 2005, the National Institute of Allergy and Infectious Disease (NIAID) and the Food Allergy and Anaphylaxis Network (FAAN) convened a consensus meeting, which included representatives from 16 different organizations from North America, Europe, and Australia, to develop a clinically useful and universally accepted definition of anaphylaxis (Table 1).
Table 1: Clinical criteria for diagnosing anaphylaxis
Anaphylaxis is highly likely when any one of the following three criteria are fulfilled:
Interestingly, the presence of cutaneous signs appears to be inversely proportional to the severity of the anaphylactic event. In two studies of fatal anaphylaxis, it was noted that less than 20% of the subjects had cutaneous findings. Allergies to peanut, tree nuts, or shellfish are more likely than other foods to cause severe reactions.
If the diagnosis of anaphylaxis cannot be definitively established, measurement of serum tryptase may be warranted. Tryptase is a neutral protease present in the secretory granules of all mast cells. The ideal time to measure serum tryptase is within three hours of the suspected anaphylaxis; however, significant elevations can be found up to six hours or longer. During anaphylaxis due to food allergy, tryptase levels can also be in the normal range, therefore, a negative test does not rule out food-induced anaphylaxis.
Diagnosis of Food Allergy
To identify an IgE-mediated reaction, the history is key. It is important to establish the temporal association of ingestion and symptoms (generally seconds to minutes, up to two hours), the type of symptoms (skin, gastrointestinal, or respiratory), the amount of food protein ingested, and the symptoms after eating similar foods. Food allergic reactions should also be consistent; each time a known food allergen is eaten in sufficient quantity, an adverse reaction would be expected. There are some exceptions to this rule. For example, up to 75% of children with milk or egg allergy can tolerate small amounts of these foods in extensively baked goods such as muffins or cakes. The same amount of milk or egg, if not extensively cooked, could produce an allergic reaction. Interestingly, roasting does not alter the allergenicity of a peanut.
If the history is concerning for food allergy, testing for allergen-specific IgE studies should be undertaken. The sensitivity and specificity of allergen-specific IgE are often estimated to be greater than 90% and approximately 50%, respectively, and depend on the allergen, the type of test, and the amount of IgE detected. Studies have been performed to define the predictive value of peanut-specific IgE for clinical use. For example, in children over 2 years of age, 2 kUA/L indicates a 50% positive predictive value for clinical allergy, and 14 kUA/L indicates a 95% predictive value.
The prevalence of peanut allergy has been increasing, and affects up to 2% of children under the age of 18. The reason for this rise is unknown, but it occurred during a period of time in which infants from allergic families were generally advised to avoid peanut consumption in early life. Current recommendations from the AAP Committee on Nutrition no longer recommend allergen avoidance as a means to prevent the onset of food allergy.
Current recommendation on prevention, recognition and treatment of food-induced anaphylaxis is built on the foundation of strict dietary avoidance, education to recognize signs and symptoms, and rapid access to treatment including injectable epinephrine. For mild reactions that are limited to the skin, administration of an antihistamine (diphenhydramine or cetirizine) can relieve symptoms. Children with mild reactions should be watched for approximately four hours, with frequent checks within that time, to monitor for worsening symptoms and evidence of anaphylaxis.
For more severe reactions (anaphylaxis), epinephrine should be administered IM in the anterior-lateral thigh and a 911 call should be placed. The patient, unless contraindicated due to vomiting or respiratory distress, should be placed in the recumbent position with the legs elevated to maximize blood return from the extremities. Physicians should also be prepared for fluid resuscitation in case of hypotension. Corticosteroids are often used for 48 hours with the hope of preventing prolonged or biphasic anaphylaxis, but there are no well-controlled trials that exist to provide an evidence-base for clear recommendations. Because of the risk of prolonged or biphasic reactions, a period of observation of three to four hours is recommended following anaphylactic reactions. If a patient is not responding to epinephrine or is still having symptoms four hours after their initial reaction they should be admitted for observation in a hospital.
Epinephrine is available in various forms, and the most commonly prescribed is the EpiPen (0.3 mg), or for children weighing less than 28 kg, the EpiPen Jr (0.15 mg). Twin dose packs are available and should be prescribed as repeat doses may be necessary. Instructions and taking time to review the mechanics of EpiPen use are paramount as a study demonstrated that only 32% of people with an EpiPen could demonstrate proper use. It is also important to give patients and families a written management plan both for acute and chronic treatment (Table 2). Educational materials are available through many organizations including the Food Allergy and Anaphylaxis Network (www.foodallergy.org).
Table 2: Food allergy action plan
1. Should contain:
2. May contain:
Natural History of Food Allergy in Children
Most food allergies in children are outgrown. Unfortunately, peanut allergy can be persistent and is outgrown in only 20% of affected children. Children whose initial reaction to peanut is relatively mild have a somewhat better prognosis. Allergen-specific IgE levels can be followed every one to three years to monitor the likelihood of an allergic reaction. Notably, the level of allergen-specific IgE is not a reliable indicator of the severity of adverse reactions. Testing for tree nuts is often advisable. In a study of 145 peanut allergic individuals, 7% also reacted to a tree nut oral challenge.
Can peanut allergy be prevented?
Interestingly, there is new evidence that infants fed a high peanut diet at an early age may have less peanut allergy. Du Toit, et al noted the rate of peanut allergy in a school-aged cohort of Israeli Jewish children was 0.17% compared to 1.85% in Jewish children in the United Kingdom. The 10-fold difference between the children in the Israel versus U.K. may be explained by the fact that Israeli infants (8-14 months of age) were more likely to routinely consume peanut protein, whereas the Jewish infants in U.K. homes did not. By 9 months of age, 69% of Israelis were eating peanut compared with only 10% of U.K. infants. A case-control study conducted in the U.K. found that early oral exposure to peanut in infants with high environmental peanut exposure may contribute to a protective effect against the development of peanut allergy, and that there was no effect of maternal peanut consumption during pregnancy or lactation on the development of peanut allergy. There are several studies underway to investigate the effects of early peanut introduction on the development of allergy. Efforts to develop a desensitization regimen for peanut allergy are also underway. One double-blind, placebo-controlled study with 28 individuals showed promising results for both safety and peanut desensitization. Larger studies are in progress to optimize the regimen and to determine whether the desensitization is temporary or permanent.
In the case described in this review, there is clear evidence of anaphylaxis, as indicated by multi-system involvement (cutaneous, respiratory, and possibly GI symptoms). Administration of epinephrine IM along with diphenhydramine are indicated, followed by close observation in an emergency department or urgent care setting. Administration of systemic corticosteroid should also be considered. Education, including a written food allergy action plan and reviewing the mechanics of epi-pen use, will help to minimize adverse reactions in the future. There is hope that our current treatment strategies may in a few years be supplemented with desensitization, and this will be especially important for peanut allergy, which tends to be both severe and persistent.
- Burks A.W., Jones S.M., Boyce J.A., Sicherer S.H., Wood R.A., Assa’ad A., Sampson H.A. NIAD-Sponsored 2010 Guidelines for Managing Food Allergy: Applications in the Pediatric Population. Pediatrics 2011 November; 128;955, Pages 955-965.
- Sampson, H. Utility of Food-specific IgE Concentrations in Predicting Symptomatic Food Allergy. Journal of Allergy and Clinical Immunology 2001 May; Volume 107, Issue 5, Pages 891-896.
- Hjalti M. Bjornsson, MD and Charles S. Graffeo, MD. Improving Diagnostic Accuracy of Anaphylaxis in the Acute Care Setting. West J Emerg Med. 2010 December; 11(5): 456–461.