Published October 20, 2010 ALLERGY Food Sensitivities: Allergy Versus Intolerance Manouchehr Saljoughian, PharmD, PhD Department of Pharmacy Service Alta Bates Summit Medical Center Berkeley, California US Pharm. 2010;35(10)HS-26-HS-31. Food allergy is defined as an adverse reaction or abnormal response to a food protein or food additive and is triggered by the body's immune system (IgE mediated). Anaphylactic reactions to food can sometimes cause serious illness and even death. Tree nuts and peanuts are the leading causes of these deadly allergic reactions (anaphylaxis). In recent decades, the prevalence of food allergy appears to have increased, and even a tiny amount of the allergy-causing food can trigger signs and symptoms such as digestive problems, hives, or swollen face and airways (angioedema). In people with celiac disease (not a true food allergy), the gluten in certain foods can initiate a complex immune response and cause severe symptoms.1 Food intolerance is also a reaction to food, but it is not mediated by the body's immune system and, therefore, it is not an allergy. The symptoms of food intolerance are less bothersome. People often confuse the two, because food intolerance also shows some of the same signs and symptoms as food allergy, such as nausea, vomiting, cramping, and diarrhea.2 Food allergy affects an estimated 4% to 8% of children under age 3 years and about 2% of adults. While there is no cure, some children outgrow their food allergy as they get older. Food allergy symptoms usually develop within a few minutes to an hour after eating the offending food. While 3.3 million Americans are allergic to peanuts or tree nuts, 6.9 million are allergic to seafood. Food allergies cause 30,000 cases of anaphylaxis, 2,000 hospitalizations, and 150 deaths annually.3 Treatment consists of either immunotherapy (desensitization) or avoidance, in which the allergic person avoids all forms of contact with the food to which he or she is allergic.3 Pathogenesis of Food Allergy It is well reported that a few specific foods cause the majority of the food reactions. The most common triggers of a food reaction in adults include peanuts, fish, shellfish, tree nuts (e.g., walnuts, pecans), and sesame. Problematic foods for children are eggs, milk (especially in infants and young children), and peanuts. Chocolate, long thought by some parents to cause food allergies in children, rarely triggers a food allergy.4 In a true food allergy, the immune system mistakenly identifies a specific food or an additive in food as a harmful substance. The immune system cells then release certain antibodies known as immunoglobulin E (IgE) to fight the allergens originating from the problematic food or food substance. The next time the smallest amount of that food is eaten, the IgE antibodies that circulate in the blood sense it and signal the immune system mast cells to release histamine and other cytokines into the bloodstream. These chemicals are responsible for a range of allergic signs and symptoms. Histamine contributes to inflammation and causes swelling on the skin and itching. It is responsible for the hives that appear on the skin when the patient is tested for allergy. These hives show the presence of IgE and are one of the best indications of allergy.5 Risk Factors Risk factors that increase the chance of food allergies include age (young children); history of eczema (it is reported that about one in three people with atopic dermatitis or eczema also have a food allergy); and family history of other types of allergies, including hay fever, asthma, and pollen.6 In many people who have hay fever, fresh fruits and vegetables and certain nuts and spices can trigger an allergic reaction that causes the mouth to tingle or itch. In some people, pollen-food allergy symptoms can cause swelling of the throat or even anaphylaxis. This kind of allergy is an example of cross-reactivity. It is believed that certain proteins in fruits and vegetables cause the reaction because they are similar to those allergy-causing proteins found in certain pollens. For example, if someone is allergic to ragweed or birch pollen, he or she may also react to melons. Cooking fruits and vegetables can help to avoid these reactions. Most cooked fruits and vegetables do not cause cross-reactive oral allergy symptoms.6 Other risk factors for severe anaphylaxis are agents or drugs that cause increased intestinal permeability--such as alcohol and aspirin, beta-blockers, and ACE inhibitors--and exercise. Histamines, released by the immune system during an allergic reaction, have been shown to trigger migraines in some people. Symptoms of Anaphylaxis Severe food allergic reaction can cause life-threatening symptoms, and emergency treatment is critical. Untreated, anaphylaxis can cause a coma or death. Serious reactions are constriction and tightening of airways; a swollen throat or a lump in throat that makes it difficult to breathe; and shock with a severe drop in blood pressure, rapid pulse and dizziness, lightheadedness, or loss of consciousness.7 In some people, exercise can trigger an allergic reaction to a food. An exercise-induced food allergy may cause itching and lightheadedness. In serious cases, it can also cause reactions such as hives or anaphylaxis. Not eating and avoiding a certain food for a couple of hours before exercise may help prevent this problem.7 Mild reactions to food are not critical and life-threatening but also require immediate medical attention. Some of these reactions are stomach cramps, pain, nausea, vomiting, diarrhea, skin rash and itching (especially hives), coughing, wheezing, shortness of breath, swelling (lips, mouth, tongue, throat), nasal congestion, and severe drop in blood pressure. Food Intolerance If after eating food a patient has digestive symptoms, chances are this is not a true food allergy but a food intolerance. Depending on the type of food intolerance, the patient may be able to eat small amounts of problem foods without a reaction. By contrast, if a patient has a true food allergy, even a tiny amount of food may trigger an allergic reaction. Sometimes, it may be difficult to distinguish food intolerance from food allergy due to the fact that some people are sensitive to a substance or ingredient used in the preparation of the food and not to the food itself. In the following cases, there is a possibility that symptoms may be mistaken for those of a true food allergy.3 Celiac Disease While celiac disease is sometimes referred to as a gluten allergy, it is not a true food allergy. Like a food allergy, it does involve an immune system response, but it is a unique immune system reaction that is more complex than a simple food allergy. Eating gluten, a protein found in bread, pasta, cookies, and many other foods containing wheat, barley, or rye, triggers this chronic digestive condition. In people with celiac disease, eating foods containing gluten will initiate an immune reaction that causes damage to the surface of the small intestine and an inability to absorb certain nutrients. Symptoms of celiac disease include diarrhea, abdominal pain, and bloating. In some cases, celiac disease causes malnutrition and nutrient deficiencies.8 Enzyme Deficiency Some patients may not have adequate amounts of certain enzymes needed to digest specific foods. Insufficient quantities of the enzyme lactase may reduce the ability to digest lactose, the main sugar in milk products. Lactose intolerance can cause bloating, abdominal cramping, diarrhea, foul-smelling stools, weight loss, and excess gas. Lactose intolerance is more common in Asian, African, African American, Native American, and Mediterranean populations than it is among northern and western Europeans. Lactose intolerance can begin at different times in life. In Caucasians, it usually starts to affect children older than 5 years. In African Americans, lactose intolerance often occurs as early as age 2 years. Food Poisoning Sometimes food poisoning can mimic an allergic reaction. Bacteria in spoiled tuna and other fish can make a toxin that triggers harmful reactions. Most cases of food poisoning are from common bacteria such as Staphylococcus species or E coli. Botulism is a very serious form of food poisoning that can be fatal. It can come from improper home canning. Certain types of mushrooms and rhubarb can also be toxic. Dehydration is the most common complication of botulism and can occur from any of the other causes of food poisoning. Food Additives Some people have digestive reactions and other allergic symptoms after eating certain food additives, such as monosodium glutamate (MSG), artificial sweeteners, and food- or medication-coloring agents, such as tartrazine in erythromycin tablets. Sulfites used to preserve dried fruit, canned foods, and wine can trigger asthma attacks in sensitive people. Irritable Bowel Syndrome Certain foods may trigger the signs and symptoms of irritable bowel syndrome (IBS). People may find that certain foods will cause cramping, constipation, or diarrhea. These foods need to be eliminated from the diet to avoid the symptoms.3 Unlike more serious intestinal diseases such as ulcerative colitis and Crohn's disease, IBS does not cause inflammation or changes in bowel tissue or increase the risk of colorectal cancer. In many cases, irritable bowel syndrome can be controlled by managing diet, lifestyle, and stress. Autism and Food Allergy Autistic disorders, first seen in early childhood, cause problems with social interaction and communication, as well as abnormal behavioral patterns. Autism is likely genetic, although there also seem to be environmental factors that influence the condition. In recent years, it has been suggested that food allergies play a role in worsening autism. Specifically, gluten (a wheat protein) and casein (a milk protein) have been blamed for worsening symptoms in children with autism. On the other hand, it is not completely clear that foods do worsen autism, although there are many theories about how this could occur. It has been suggested that autism could be due to the loss of regulation of the immune system's white blood cells, which would, in turn, trigger certain chemicals (cytokines) that cause the neurologic abnormalities seen in children with autism. With regard to food, a recent well-designed, but small, study showed some improvement in autistic traits in the children receiving a gluten-free/casein-free diet.9 Studies of larger numbers of children are needed to confirm the results of this small study. Tests and Diagnosis A systematic approach to diagnosis includes a careful history, followed by laboratory studies, elimination diets, and often food challenges to confirm a diagnosis. A clinical allergist is in the best position to diagnose food allergy. The allergist will review the patient's history and the symptoms or reactions that have been reported after food ingestion. If the symptoms or reactions are consistent with food allergy, allergy tests will be performed (TABLE 1). Many food allergens have been characterized at a molecular level, which has increased our understanding of the immunopathogenesis of food allergy and might soon lead to novel diagnostic and therapeutic approaches. Currently, management of food allergies consists of educating the patient to avoid ingesting the responsible allergen and to initiate therapy in case of an unintended ingestion. Treatments The only way to prevent an allergic reaction is to avoid the foods that cause signs and symptoms. However, despite their best efforts, people may come into contact with a food that causes a reaction. Minor Allergic Reaction In these cases, OTC or prescribed antihistamines such as diphenhydramine (Benadryl) may help reduce symptoms. These drugs can be taken after exposure to an allergy-causing food to help relieve skin redness, itching, or hives. However, antihistamines cannot treat a severe allergic reaction. Severe Allergic Reaction In these cases, patients may need an emergency injection of epinephrine and a trip to the emergency room. Many people with allergies carry an autoinjector (EpiPen, EpiPen Jr, or Twinject). This device is a combined syringe and concealed needle that injects a single dose of medication when pressed against the thigh. People have to make sure to know how to use the autoinjector. Also, it is important that people closest to the patient know how to administer the drug; in these cases they can help in an anaphylactic emergency and could save a life. Corticosteroid medications have also been used for more severe swelling and itching.6 Prevention and Recommendations The best way to prevent an allergic reaction is to identify and avoid foods that trigger it. For some people, this is a mere inconvenience, but others find it a greater hardship. Also, some foods--when used as ingredients in certain dishes--may be well hidden. This is especially true in restaurants.3 While there is ongoing research to find better treatments to reduce food allergy symptoms and prevent allergy attacks, proven treatment exists that can prevent or completely relieve symptoms. Unfortunately, allergy shots (immunotherapy), a series of injections used to reduce the effect of other allergies such as hay fever, are not effective for treating food allergies. The key treatment is to avoid the food in question, and to work with the doctor to learn how to relieve the symptoms and how to identify and respond to a severe reaction. People should always read the label on a manufactured food to make sure it does not contain an ingredient they are allergic to. Even if the person thinks he or she knows what is in a food, the label should be checked. Ingredients sometimes change. Food labels are required to clearly list whether they contain any common food allergens. Patients should read food labels carefully to avoid these top eight sources of food allergy: milk, eggs, peanuts, tree nuts, fish, shellfish, soy, and wheat. At restaurants and social gatherings, there is always a risk that a person might eat a food he or she is allergic to. Many people do not understand the seriousness of an allergic food reaction and may not realize that a tiny amount of a food can cause a severe reaction. If there is any suspicion at all that a food may contain an allergen, it should not be eaten.3 REFERENCES 1. Sicherer SH, Sampson HA. Food allergy. J Allergy Clin Immunol. 2006;117:S470-S475. 2. Moneret-Vautrin DA, Morisset M. Adult food allergy. Curr Allergy Asthma Rep. 2005;5:80-85. 3. Centers for Disease Control and Prevention. Food allergies. www.cdc.gov/healthyyouth/ foodallergies. 4. Ben-Shoshan M, Kagan RS, Alizadehfar R, et al. Is the prevalence of peanut allergy increasing? A 5-year follow-up study in children in Montreal. J Allergy Clin Immunol. 2009;123:783-788. 5. Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009;124:3-20;quiz 21-22. 6. Bock SA, Muñoz-Furlong A, Sampson HA. Letter to editor: further fatalities caused by anaphylactic reactions to food, 2001-2006. J Allergy Clin Immunol. 2007;119:1016-1018. 7. Chapman JA, Bernstein L, Lee RE, Oppenheimer J. Food allergy: a practice parameter. Ann Allergy, Asthma Immunol. 2006;96:S1-S68. 8. Lee A, Newman JM. Celiac diet: its impact on quality of life. J Am Dietetic Assoc. 2003;103: 1533-1535. 9. Croen LA, Grether JK, Yoshida CK, et al. Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders. Arch Pediatr Adolesc Med. 2005;159:151-157. 10. Hill DJ, Heine RG, Hosking CS. The diagnostic value of skin prick testing in children with food allergy. Pediatr Allergy Immunol. 2004;15:435-441. To comment on this article, contact rdavidson@uspharmacist.com.