The New Insight Differential diagnosis of Food Allergy

Adverse immune responses to foods affect approximately 5% of young children and 3% to 4% of adults in the world and appear to have increased in prevalence. Food allergy is an immune-based disease that has become a serious health concern around the world. A recent study estimates that food allergy affects 5% of children under the age of 5 years and 4% of teens and adults, and its prevalence appears to be on the increase. Food-induced allergic reactions are responsible for a variety of symptoms and disorders involving the skin and gastrointestinal and respiratory tracts and can be attributed to IgE-mediated and non–IgE-mediated (cellular) mechanisms. Genetic disposition and environmental factors might abrogate oral tolerance, leading to food allergy. Disease outcomes are influenced by the characteristics of the immune response and of the triggering allergen. Diagnosis is complicated by the observation that detection of food-specific IgE (sensitization) does not necessarily indicate clinical allergy. Therefore diagnosis requires a careful medical history, laboratory studies, and, in many cases, an oral food challenge to confirm a diagnosis. Novel diagnostic methods, including ones that focus on immune responses to specific food proteins or epitopes of specific proteins, are under study. Currently, management of food allergies consists of educating the patient to avoid ingesting the responsible allergen and to initiate therapy (eg, with injected epinephrine for anaphylaxis) in case of an unintended ingestion. Improved therapeutic strategies under study include oral and sublingual immunotherapy, Chinese herbal medicine, anti-IgE antibodies, and modified vaccines.

The symptoms of this disease can range from mild to severe and, in rare cases, can lead to anaphylaxis, a severe and potentially life-threatening allergic reaction. There are no therapies available to prevent or treat food allergy: the only prevention option for the patient is to avoid the food allergen, and treatment involves the management of symptoms as they appear. And because the most common food allergens—eggs, milk, peanuts, tree nuts, soy, wheat, crustacean shellfish, and fish—are highly prevalent, patients and their families must remain constantly vigilant.

Food allergy is an increasingly prevalent problem in westernized countries, and there is an unmet medical need for an effective form of therapy. A number of therapeutic strategies are under investigation targeting foods that most frequently provoke severe IgE-mediated anaphylactic reactions (peanut, tree nuts, and shellfish) or are most common in children, such as cow’s milk and hen’s egg. Approaches being pursued are both food allergen specific and nonspecific. Allergen-specific approaches include oral, sublingual, and epicutaneous immunotherapy (desensitization) with native food allergens and mutated recombinant proteins, which have decreased IgE-binding activity, coadministered within heat-killed Escherichia coli to generate maximum immune response. Diets containing extensively heated (baked) milk and egg represent an alternative approach to food oral immunotherapy and are already changing the paradigm of strict dietary avoidance for patients with food allergy. Nonspecific approaches include monoclonal anti-IgE antibodies, which might increase the threshold dose for food allergen in patients with food allergy, and a Chinese herbal formulation, which prevented peanut-induced anaphylaxis in a murine model and is currently being investigated in clinical trials. The variety of strategies for treating food allergy increases the likelihood of success and gives hope that accomplishing an effective therapy for food allergy is within reach.

Types of adverse reactions to food

Differential diagnosis of food allergy

In a meta-analysis of studies evaluating the prevalence of FA, up to 35% of individuals reporting a reaction to food believe they have FA, whereas studies confirming FA by oral food challenge suggest a much lower prevalence of about 3.5%. Much of this discrepancy is due to a misclassification of adverse reactions to foods that are not allergic in origin, for example lactose intolerance causing bloating, abdominal pain, and diarrhea after consuming milk products. Many causes of reactions to foods are not allergic in origin.

In the differential diagnosis of FAs, allergic disorders from other causes, such as drugs, as well as disorders that are not immunologic in nature, must be considered. The patient’s medical history is vital in excluding these alternative diagnoses. For example:

  • Acute allergic reactions initially attributed to a food may be triggered by other allergens (for example, medications, insect stings).
  • In children with AD, eczematous flares erroneously attributed to foods are sometimes precipitated by irritants, humidity, temperature fluctuations, and bacterial infections of the skin (for example, Staphylococcus aureus).
  • Chronic GI symptoms may result from reflux, infection, anatomical disorders, metabolic abnormalities (for example, lactose intolerance), and other causes.
  • Chemical effects and irritant effects of foods may mimic allergic reactions. For example, gustatory rhinitis may occur from hot or spicy foods due to neurologic responses to temperature or capsaicin.
  • Tart foods may trigger an erythematous band on the skin of the cheek along the distribution of the auriculotemporal nerve in persons with gustatory flushing syndrome.
  • Food poisoning due to bacterial toxins, such as toxigenic E. coli, or scombroid poisoning caused by spoiled dark-meat fish, such as tuna and mahi-mahi, can mimic an allergic reaction.
  • For persons with EGIDs, alternative diagnoses such as parasite infections, gastroesophageal reflux disease, systemic eosinophilic disorders, and vasculitis should be considered.
  • Behavioral and mental disorders may result in food aversion (for example, anorexia nervosa, bulimia, and Munchausen syndrome by proxy).
  • Pharmacologic effects of chemicals that occur in foods (for example, tryptamine in tomatoes) and food additives may mimic some allergic symptoms of the skin and GI tract.

References:

  • Hugh A. Sampson, Scott H. Sicherer. The Journal of Allergy and Clinical Immunology Volume 125, Issue 2, Supplement 2, Pages S116-S125, February 2010 Food allergy.
  • Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel. NIAID-Sponsored Expert Panel. 2010
  • Branum AM, Lukacs SL. Food allergy among children in the United States. Pediatrics. 2009 Dec;124(6):1549–1555
  • Chapman JA, Bernstein IL, Lee RE, Oppenheimer J, chief editors. Food allergy: A practice parameter. Ann Allergy Asthma Immunol. 2006 Mar;96(3 Suppl. 2):S1-68.
  • Chafen JJ, Newberry S, Riedl M, Bravata DM, Maglione M, Suttorp M, et al. RAND Corporation. Prevalence, natural history, diagnosis, and treatment of food allergy: a systematic review of the evidence. RAND working paper, prepared for the National Institute of Allergy and Infectious Diseases. Santa Monica (CA): RAND Corporation; 2010.

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