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SUCCESS WITH FOOD ALLERGY AND INTOLERANCE Janice Joneja Ph.D., RD Food Allergy & Food Intolerance DEFINITIONS: Food Allergy Food Intolerance A generic term An immunologic describing an abnormal reaction resulting physiological response from the ingestion to an ingested food or of a food or food additive which is food additive not immunogenic 2 Symptoms of Food Allergy Controversy among practitioners because there are no definitive tests for food allergy Symptoms appear in diverse organ systems: Skin and mucous membranes Digestive tract Respiratory tract Systemic (anaphylaxis) Symptoms in nervous system are considered more subjective and sometimes may be dismissed as fictitious or psychosomatic 3 Examples of Allergic Conditions and Symptoms Skin and Mucous Membranes Atopic dermatitis (eczema) Urticaria (hives) Angioedema (swelling of tissues, especially mouth and face) Pruritus (itching) Contact dermatitis (rash in contact with allergen) Oral symptoms (irritation and swelling of tissues around and inside the mouth) Oral allergy syndrome 4 Examples of Allergic Conditions and Symptoms Digestive Tract Diarrhea Constipation Nausea and Vomiting Abdominal bloating and distension Abdominal pain Indigestion (heartburn) Belching 5 Examples of Allergic Conditions and Symptoms Respiratory Tract Seasonal or perennial rhinitis (hayfever) Rhinorrhea (runny nose) Allergic conjunctivitis (itchy, watery, reddened eyes) Serous otitis media (earache with effusion) [“gum ear”; “glue ear”] Asthma Laryngeal oedema (throat tightening due to swelling of tissues) 6 Examples of Allergic Conditions and Symptoms Nervous System Migraine Other headaches Spots before the eyes Listlessness Hyperactivity Lack of concentration Tension-fatigue syndrome Irritability Chilliness Dizziness 7 Examples of Allergic Conditions and Symptoms Other Urinary frequency Bed-wetting Hoarseness Muscle aches Low-grade fever Excessive sweating Pallor Dark circles around the eyes 8 Anaphylaxis Severe reaction of rapid onset, involving most organ systems, which results in circulatory collapse and drop in blood pressure In the most extreme cases the reaction progresses to anaphylactic shock with cardiovascular collapse This can be fatal 9 Anaphylaxis Usual progress of reaction Burning, itching and irritation of mouth and oral tissues and throat Nausea, vomiting, abdominal pain, diarrhea Feeling of malaise, anxiety, generalized itching, faintness, body feels warm Nasal irritation and sneezing, irritated eyes Hives, swelling of facial tissues, reddening Chest tightness, bronchospasm, hoarseness Pulse is rapid, weak, irregular, difficult to detect Loss of consciousness Death may result from suffocation, cardiac arrhythmia, or shock 10 Foods and Anaphylaxis Almost any food can cause anaphylactic reaction Some foods more common than others: Peanut Tree nuts Shellfish Fish Egg In children under three years Cow’s milk Egg Wheat Chicken 11 Exercise-induced Anaphylaxis Usually occurs within two hours of eating the allergenic food Onset during physical activity Foods most frequently reported to have induced exercise-induced anaphylaxis: Wheat (omega-5-gliadin) and other grains Celery and other vegetables Shellfish (shrimp; oysters) Chicken Squid Peaches and other fruits Nuts especially hazelnut Peanuts and soy beans May be associated with aspirin ingestion 12 Emergency Treatment for Anaphylactic Reaction Injectable adrenalin (epinephrine) Fast-acting antihistamine (e.g. Benadryl) Usually in form of TwinJect® or Epipen® Transport to hospital immediately Second phase of reaction is sometimes fatal, especially in an asthmatic Patient may appear to be recovering, but 2-4 hours later symptoms increase in severity and reaction progresses rapidly 13 Immunologically Mediated Reactions IgE-mediated: Immediate onset (anaphylaxis) Oral allergy syndrome (OAS) Latex-Food syndrome Non-IgE-mediated Eosinophilic gastrointestinal diseases Food protein-sensitive enteropathies Gluten-sensitive enteropathy (celiac disease) 14 Role of the Dietitian Accurate identification of the foods responsible Elimination and challenge to confirm or refute: allergy tests suspected allergens and intolerance triggers Directives for avoidance of the culprit foods Recognition of sources of the offenders Understanding new labelling laws 15 The Dietitian’s Role Provide guidelines and resources to ensure complete balanced nutrition from alternative foods Directives for prevention of food allergy and induction of oral tolerance Macronutrients Micronutrients New guidelines Ensure freedom from allergens in food provision and preparation services 16 Tests for Adverse Reactions to Foods Rationale and Limitations Skin Tests: Value in Practice Positive predictive accuracy of skin tests rarely exceeds 50% Many practitioners rate them lower Negative skin tests do not rule out the possibility of non-IgE-mediated reactions Do not rule out non-immune-mediated food intolerances 18 Value of Skin Tests in Practice Tests for highly allergenic foods thought to have close to 100% negative predictive accuracy for diagnosis of IgE-mediated reactions Such foods include: Egg Milk Fish Wheat Tree nuts Peanut 19 Blood Tests RAST: radioallergosorbent test (e.g. ImmunoCap-RAST; Phadebas-RAST) FAST; Fluorescence allergosorbent test ELISA: enzyme-linked immunosorbent assay Designed to detect and measure levels of allergen-specific antibodies Used for detection of levels of allergen-specific IgE May measure total IgE - thought to be indicative of “atopic potential” Some practitioners measure IgG (especially IgG4) by ELISA 20 Value of Blood Tests in Practice Blood tests have about the same sensitivity as skin tests for identification of IgE-mediated sensitisation to food allergens There is often poor correlation between high level of anti-food IgE and symptoms when the food is eaten Many people with clinical signs of food allergy show no elevation in IgE Reasons for failure of blood tests to indicate foods responsible for symptoms are the same as those for skin tests 21 Value of Blood Tests in Practice Anti-food antibodies (especially IgG) are frequently detectable in all humans, usually without any evidence of adverse effect IgG production is likely to be the first stage of development of oral tolerance to a food Studies suggest that IgG4 indicates protection or recovery from IgE-mediated food allergy 22 Tests for Intolerance of Food Additives There are no reliable skin or blood tests to detect food additive intolerance Skin prick tests for sulphites are sometimes positive A negative skin test does not rule out sulphite sensitivity History and oral challenge provocation of symptoms are the only methods for the diagnosis of additive sensitivity at present Caution: Challenge may occasionally induce anaphylaxis in sulphite-sensitive asthmatics 23 Commercial Testing and Food Allergy Management Programs LEAP (Lifestyle Eating and Performance); Signet Diagnostic Corporation Claims to “successfully treat … IBS, migraines, fibromyalgia, autism, ADD/ADHD, IBD, urticaria, chronic fatigue syndrome, obesity, etc.” Negative aspects: Testing based on “mediator release” Not a recognized accurate method for allergy testing Positive aspects Management includes elimination and challenge, food substitutions and meal planning 24 Commercial Testing and Food Allergy Management Programs Gemoscan Corporation: HEMOCODE™ (Gemoscan) Food Intolerance System, and MenuWise™ Food Intolerance Plan “personalized naturopathic nutritional programs that promote wellbeing.” Available in retail stores (Rexall and Loblaws) Price is $450 for 250 foods Tests identify IgG antibody to foods Customers receive support from pharmacist/naturopath, including consultation on appropriate vitamins and supplements Negative aspects There is no provision for dietetic counselling and thus a high risk for nutritional deficiency when the “reactive foods” are eliminated without sufficient knowledge to provide nutrients from alternate sources 25 Unorthodox Tests Many people turn to unorthodox tests when avoidance of foods positive by conventional test methods have been unsuccessful in managing their symptoms Tests include: Vega test (electro-dermal) Biokinesiology (muscle strength) Analysis of hair, urine, saliva Radionics ALCAT (lymphocyte cytotoxicity) 26 Drawbacks of Unreliable Tests Diagnostic inaccuracy Therapeutic failure False diagnosis of allergy Creation of fictitious disease entities Failure to recognize and treat genuine disease Inappropriate and unbalanced diets Risk of nutritional deficiencies and dietrelated disease 27 Non-IgE-Mediated Allergies Eosinophilic Gastrointestinal Diseases Food Protein Induced Enteropathies Eosinophilic Gastrointestinal Diseases (EGID) Expanded definition of food allergy now encompasses any immunological response to food components that results in symptoms when the food is consumed Example is group of conditions in the digestive tract in which infiltration of eosinophils is diagnostic Collectively these diseases are becoming known as eosinophilic gastrointestinal diseases (EGID). 29 Characteristics of EGID Inflammatory mediators are released from the eosinophils, and act on local tissues in the esophagus and gastrointestinal tract, causing inflammation In eosinophilic digestive diseases there is no evidence of IgE, therefore tests for IgEmediated allergy are usually negative Unless there is a concomitant IgE-mediated reaction to food 30 Eosinophilic Esophagitis Symptoms most frequently associated with EO and considered to be typical of the disease include: Vomiting Regurgitation of food Difficulty in swallowing: foods are said to be sticking on the way down Choking on food Heartburn and chest pain Water brash (regurgitation of a watery fluid not containing food material) Poor eating Failure to thrive (poor or no weight gain, or weight loss) 31 Eosinophilic Esophagitis Although the symptoms resemble gastroesophageal reflux disease (GERD), the reflux of EO dose not respond to the medications used to suppress the gastric acid and control regurgitation (antireflux therapy) in GERD There is emerging data to suggest that use of acid-suppressing medications may predispose patients to the development of EoE 32 Diagnosis of EoE Three criteria must be met: Clinical symptoms of esophageal dysfunction Oesophageal biopsy with an eosinophil count of at least 15 eosinophils per highpower (x400 mag) microscopy field Exclusion of other possible causes of the condition Dellon ES 2013 33 Eosinophilic Esophagitis Foods most frequently implicated in Children Egg Cow’s milk Soy Wheat Corn Peanuts Tree nuts Shellfish Fish Beef Rye 34 Six-Food Elimination Diet and EoE Adult study 2013 Foods eliminated: Cereals Wheat Rice Corn Milk and milk products Eggs Fish and seafood Legumes including peanuts Soy Lucendo et al 2013 35 Six-Food Elimination Diet and EoE Indicators of positive outcome: Reduced eosinophil count: 73.1% of subjects Maintained remission for 3 years Incidence of single triggering factors: Biopsy eosinophil count (< 15/hpf) Negative gastro-oesophageal reflux Cow’s milk 61.9% Wheat 28.6% Eggs 26.2% Legumes 23.8% No correlation with allergy tests 36 Eosinophilic Gastroenteritis: Diagnosis by biopsy: Abnormal number of eosinophils in the stomach and small intestine Foods most frequently implicated Egg Cow’s milk Soy Wheat Peanuts Tree nuts Shellfish Fish 37 Eosinophilic Proctocolitis Diagnosis by biopsy: Abnormal number of Eosinophils confined to the colon Foods most frequently implicated Cow’s milk Soy proteins Most frequently develops within the first 60 days of life Is a non-IgE-mediated condition 38 Food Protein Enteropathies Increasing recognition of a group of non-IgEmediated food-related gastrointestinal problems associated with delayed or chronic reactions Conditions include: Food protein induced enterocolitis syndrome (FPIES) Food protein induced proctocolitis (FPIP) These digestive disorders tend to: Appear in the first months of life Be generally self-limiting Typically resolve at about two years of age 39 FPIES Symptoms Symptoms in infants typically include: Profuse vomiting Diarrhoea, which can progress to dehydration and shock in severe cases Increased intestinal permeability Malabsorption Dysmotility Abdominal pain Failure to thrive (typically weight gain less than 10 g/day) In severe episodes the child may be hypothermic (<36 degrees C) 40 FPIES Characteristics Triggered by foods, but not mediated by IgE Condition typically develops in response to food proteins as a result of digestive tract and immunological immaturity Cow’s milk and soy proteins, usually given in infant formulae, reported as most frequent causes Milk and soy-associated FPIES usually starts within the first year of life; most frequently within the first six or seven months When solids foods are introduced, other foods may cause the condition Recent research claims that rice is the most common food causing FPIES 41 Foods Associated with FPIES Removal of the culprit foods usually leads to immediate recovery from the symptoms Foods that have been identified as triggers of FPIES in individual cases include: Milk Cereals (oats, barley and rice) Legumes (peas, peanuts, soy, lentils) Vegetables (sweet potato, squash) Poultry (chicken, turkey) Egg 42 Prevention of FPIES Most reports of FPIES indicate that exclusive breast-feeding is protective in potential cases of FPIES None of the infants who later developed FPIES after the introduction of solids had symptoms while being exclusively breast-fed Authors of these studies suggest that babies with FPIES while being breast-fed were sensitized to the proteins through an infant formula given during a period of immunological susceptibility 43 Diagnosis and Management of FPIES There are no diagnostic tests for FPIES at present Indicators include clinical presentation : development of acute symptoms immediately after consumption of the offending foods (often milk- or soy-based infant formula) absence of positive tests for food allergy Elimination and challenge with the suspect foods will usually confirm the syndrome 44 Diagnosis and Management of FPIES Removal of the offending food leads to symptom resolution In most cases delayed introduction of solid foods is advised because of the possibility that until the child’s immune system has matured, a similar reaction to proteins in other foods may elicit the same response 45 Food Protein Induced Proctitis/Proctocolitis Blood in the stool is typical Condition typically appears in the first few months of life, on average at the age of two months The absence of other symptoms, such as vomiting, diarrhoea, and lack of weight gain (failure to thrive) usually rules out other causes such as food allergy, and food protein enteropathies Usually the blood loss is very slight, and anaemia as a consequence of loss of blood is rare Diagnosis is usually made after other conditions that could account for the blood, such as anal fissure and infection, have been ruled out 46 Food Triggers of FPIP Most common triggers of FPIP include: Cow’s milk proteins Soy proteins Occasionally egg Many babies develop the symptoms during breast-feeding in response to milk and soy in the mother’s diet 47 Causes and Management of FPIP The cause of FPIP is unknown, but does not involve IgE, so all tests for allergy are usually negative In most cases, avoidance of the offending food leads to a resolution of the problem When the baby is breast-fed, elimination of milk and soy from the mother’s diet is usually enough to resolve the infant’s symptoms Occasionally egg can cause the symptoms, in which case, mother must avoid all sources of egg in her diet as well 48 Progression of FPIP In most cases, the disorder will resolve by the age of 1 or 2 years After this age, the offending foods may be reintroduced gradually, with careful monitoring for the reappearance of blood in the baby’s stool 49 Elimination and Challenge Protocols Identification of Allergenic Foods Removal of the suspect foods from the diet, followed by reintroduction is the only way to: Identify the culprit food components Confirm the accuracy of any allergy tests Long-term adherence to a restricted diet should not be advocated without clear identification of the culprit food components 51 Food Intolerance: Clinical Diagnosis Elimination Diet: Avoid Suspect Food Increase Restrictions Symptoms Disappear Symptoms Persist Reintroduce Foods Sequentially or Double-blind Symptoms Provoked Diagnosis Confirmed No Symptoms Diagnosis Not Confirmed 52 Elimination and Challenge Stage 1: Exposure Diary Record each day, for a minimum of 5-7 days: All foods, beverages, medications, and supplements ingested Composition of compound dishes and drinks, including additives in manufactured foods Approximate quantities of each The time of consumption 53 Exposure Diary (continued) All symptoms graded on severity: 1 (mild); 3 (moderate) Time of onset How long they last 2 (mild-moderate) 4 (severe) Record status on waking in the morning. Was sleep disturbed during the night, and if so, was it due to specific symptoms? 54 Elimination Diet Based on: Detailed medical history Analysis of Exposure Diary Any previous allergy tests Foods suspected by the patient Formulate diet to exclude all suspect allergens and intolerance triggers Provide excluded nutrients from alternative sources Duration: Usually four weeks 55 Selective Elimination Diets Certain conditions tend to be associated with specific food components Suspect food components are those that are probable triggers or mediators of symptoms Examples: Eczema: Migraine: Urticaria/angioedema: Chronic diarrhea: Asthma: Latex allergy: Oral allergy syndrome: Highly allergenic foods Biogenic amines Histamine Carbohydrates; Disaccharides Cyclo-oxygenase inhibitors Sulphites Foods with structurally similar antigens to latex Foods with structurally similar antigens to pollens 56 Few Foods Elimination Diet When it is difficult to determine which foods are suspects a few foods elimination diet is followed Limited to a very small number of foods and beverages Limited time: 10-14 days for an adult 7 days maximum for a child If all else fails use elemental formulae: May use extensively hydrolysed formula for a young child 57 Expected Results of Elimination Diet Symptoms often worsen on days 2-4 of elimination By day 5-7 symptomatic improvement is experienced Symptoms disappear after 10-14 days of exclusion 58 Challenge Double-blind Placebo-controlled Food Challenge (DBPCFC) Lyophilized (freeze-dried) food is disguised in gelatin capsules Identical gelatin capsules contain a placebo (glucose powder) Neither the patient nor the supervisor knows the identity of the contents of the capsules Positive test is when the food triggers symptoms and the placebo does not 59 Challenge (continued) Drawback of DBPCFC Expensive in time and personnel Capsule may not provide enough food to elicit a positive reaction Patient may be allergic to gelatin in capsule May be other factors involved in eliciting symptoms, e.g. taste and smell 60 Challenge (continued) Single-blind food challenge (SBFC) Supervisor knows the identity of the food; patient does not Food is disguised in a strong-tasting “inert” food tolerated by the patient: lentil soup apple sauce tomato sauce 61 Challenge Phase continued Open food challenge Sequential Incremental Dose Challenge (SIDC) Each food component is introduced separately Starting with a small quantity and increasing the amount according to a specific schedule This is usually employed when the symptoms are mild, and the patient has eaten the food in the past without a severe reaction Any food suspected to cause a severe or anaphylactic reaction should only be challenged in suitably equipped medical facility 62 Open Food Challenge Each food or food component is introduced individually The basic elimination diet, or therapeutic diet continues during this phase If an adverse reaction to the test food occurs at any time during the test STOP. Wait 48 hours after all symptoms have subsided before testing another food 63 Incremental Dose Challenge Day 1: Consume test food between meals Morning: Eat a small quantity of the test food Wait four hours, monitoring for adverse reaction If no symptoms: Afternoon: Eat double the quantity of test food eaten in the morning Wait four hours, monitoring for adverse reaction If no symptoms: Evening: Eat double the quantity of test food eaten in the afternoon 64 Incremental Dose Challenge (continued) Day 2: Do not eat any of the test food Continue to eat basic elimination diet Monitor for any adverse reactions during the night and day which may be due to a delayed reaction to the test food 65 Incremental Dose Challenge (continued) Day 3: If no adverse reactions experienced Proceed to testing a new food, starting Day 1 If the results of Day 1 and/or Day 2 are unclear : Repeat Day 1, using the same food, the same test protocol, but larger doses of the test food Day 4: Monitor for delayed reactions as on Day 2 66 Sequential Incremental Dose Challenge Continue testing in the same manner until all excluded foods, beverages, and additives have been tested For each food component, the first day is the test day, and the second is a monitoring day for delayed reactions 67 Maintenance Diet Final Diet Must exclude all foods and additives to which a positive reaction has been recorded Must be nutritionally complete, providing all macro and micro-nutrients from non-allergenic sources There is no benefit from a rotation diet in the management of food allergy A rotation diet may be beneficial when the condition is due to dose-dependent food intolerance 69 IMPORTANT NUTRIENTS IN COMMON ALLERGENS Minerals Milk Calcium + Phosphorus + Egg Peanut + Tree Nuts Seeds Soy Fish + + + + + + + + Shell fish Iron + + + + + + Zinc + + + + + + + + + + + + + + + + Magnesium Selenium Potassium + + + + Molybdenum Manganese Corn + + + + + + + + + + Chromium Copper Wheat + + + + + + + + + + + 70 Vitamins Milk Egg A + + Biotin + + Folate + + + Niacin Pantothenic acid + B6 (Pyridoxine) Nuts Seeds Soy + Fish Shellfish + + Wheat Corn + + + + + + + + + + + + + + + + + + + + Thiamin Riboflavin Peanut + + + + + + + + + + + + D + + + + E + + K + + + + + + + + + + B12 + + + + 71 Summary Food Allergy: Immune system response Food Intolerance: Usually metabolic dysfunction Diagnostic Laboratory Tests: Often ambiguous because different physiological mechanisms are involved in triggering symptoms 72 Summary Reliable tests for the detection of adverse reactions to foods: Elimination and Challenge Final diet Must provide complete nutrition while avoiding all of the foods and food components that elicit symptoms on challenge 73