SUCCESS WITH FOOD ALLERGY AND INTOLERANCE Janice Joneja Ph.D., RD J.M.Joneja, Ph.D. 2013

Food Allergy & Food Intolerance DEFINITIONS: A generic term describing an abnormal physiological response to an ingested food or food additive which is not immunogenic Food Allergy An immunologic reaction resulting from the ingestion of a food or food additive J.M.Joneja, Ph.D. 2013

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 J.M.Joneja, Ph.D. 2013

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

Examples of Allergic Conditions and Symptoms Digestive Tract Diarrhea Constipation Nausea and Vomiting Abdominal bloating and distension Abdominal pain Indigestion (heartburn) Belching

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)

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

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

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

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

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 Wheat Chicken

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

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

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)

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

The Dietitian’s Role Provide guidelines and resources to ensure complete balanced nutrition from alternative foods Macronutrients Micronutrients Directives for prevention of food allergy and induction of oral tolerance New guidelines Ensure freedom from allergens in food provision and preparation services

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 J.M.Joneja, Ph.D. 2013

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 J.M.Joneja, Ph.D. 2013

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

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

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

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

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

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 well-being.”  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

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) J.M.Joneja, Ph.D. 2013

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 diet-related disease J.M.Joneja, Ph.D. 2013

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).

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 IgE-mediated allergy are usually negative Unless there is a concomitant IgE-mediated reaction to food

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)

Eosinophilic Esophagitis Although the symptoms resemble gastro-esophageal 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

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 high-power (x400 mag) microscopy field Exclusion of other possible causes of the condition Dellon ES 2013

Eosinophilic Esophagitis Foods most frequently implicated in Children Egg Cow’s milk Soy Wheat Corn Peanuts Tree nuts Shellfish Fish Beef Rye J.M.Joneja, Ph.D. 2013

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

Six-Food Elimination Diet and EoE Indicators of positive outcome: Biopsy eosinophil count (< 15/hpf) Negative gastro-oesophageal reflux Reduced eosinophil count: 73.1% of subjects Maintained remission for 3 years Incidence of single triggering factors: Cow’s milk 61.9% Wheat 28.6% Eggs 26.2% Legumes 23.8% No correlation with allergy tests

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 J.M.Joneja, Ph.D. 2013 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 J.M.Joneja, Ph.D. 2013

Food Protein Enteropathies Increasing recognition of a group of non-IgE-mediated 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

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)

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

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

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

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

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

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

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

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

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

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 J.M.Joneja, Ph.D. 2013

Food Intolerance: Clinical Diagnosis Elimination Diet: Avoid Suspect Food Increase Restrictions Symptoms Disappear Symptoms Persist Reintroduce Foods Sequentially or Double-blind Symptoms Provoked No Symptoms Diagnosis Confirmed Diagnosis Not Confirmed J.M.Joneja, Ph.D. 2013

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 J.M.Joneja, Ph.D. 2013

Exposure Diary (continued) All symptoms graded on severity:  1 (mild);  2 (mild-moderate)  3 (moderate)  4 (severe) Time of onset How long they last Record status on waking in the morning. Was sleep disturbed during the night, and if so, was it due to specific symptoms? J.M.Joneja, Ph.D. 2013

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 J.M.Joneja, Ph.D. 2013

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: Highly allergenic foods Migraine: Biogenic amines Urticaria/angioedema: Histamine Chronic diarrhea: Carbohydrates; Disaccharides Asthma: Cyclo-oxygenase inhibitors Sulphites Latex allergy: Foods with structurally similar antigens to latex Oral allergy syndrome: Foods with structurally similar antigens to pollens

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

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 J.M.Joneja, Ph.D. 2013

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

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

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

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

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

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 Evening: Eat double the quantity of test food eaten in the afternoon J.M.Joneja, Ph.D. 2013

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 J.M.Joneja, Ph.D. 2013

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 J.M.Joneja, Ph.D. 2013

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

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 J.M.Joneja, Ph.D. 2013

IMPORTANT NUTRIENTS IN COMMON ALLERGENS Minerals Milk Egg Peanut Tree Nuts Seeds Soy Fish Shell fish Wheat Corn Calcium + Phosphorus Iron Zinc Magnesium Selenium Potassium Molybdenum Chromium Copper Manganese

Vitamins Milk Egg Peanut Nuts Seeds Soy Fish Shellfish Wheat Corn A + Biotin Folate Thiamin Riboflavin Niacin Pantothenic acid B6 (Pyridoxine) B12 D E K

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 J.M.Joneja, Ph.D. 2013

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