Kari C. Nadeau, MD, PhD Division of Allergy , Immunology, and Rheumatology at Stanford Describe the pathophysiology, initial evaluation & management of patients with food allergy including gastrointestinal food allergy, oral allergy syndrome and type I food allergy Identify recent advances in the field of food allergy and have some familiarity with published guidelines for managing food allergy Outline current and emerging treatment modalities for food allergic patients Nothing to disclose ID: 9.5 y.o. male with a history of severe food allergies, eczema, and asthma CC: Presents to PICU with hypoxic brain injury due to anaphylaxis from cow’s milk ingestion Transferred to PICU from outside hospital after multiple failed resuscitations over a 3 hr period On the evening of 8-11-04, patient accidentally drank from his sister’s cup of cow’s milk on the way to bed. He immediately developed emesis and became SOB; parents gave Epipen jr. to his thigh and called 911 Paramedics arrived in 10-15 minutes On the scene, intubation was attempted but difficult Duration of code=1 hr. CT scan showed hypoxic injury and right uncal herniation. In 2001, he presented to LPCH AAI clinic and had severe eczema and asthma. RAST tests were performed at 2001 and showed IgE > 2000, Milk> 100, Peanut>100, Egg 40.3, Soy 17.9, Wheat 20.2, Corn 26.3, Oat 12.3. No known allergies to beef. He had had one prior visit to the ER for milk ingestion in 2001. He presented with hyperventilation and emesis. He was given benadryl and his symptoms improved. He was hospitalized three times in the first year of life for asthma; no intubations but did need steroids Patient and family were prescribed an Epipen jr. and taught about anaphylaxis precautions Patient then began to receive care at private AI facility and was recommended 9 months prior to event to repeat RAST testing. This was not done. Over the past couple of months prior to event, parents decided to allow him to eat wheat, corn, oat, and egg products since he did not seem to have any symptoms from these foods. Background Definition Clinical signs and symptoms Natural History . Cow’s milk, hen’s egg, soy, peanut, tree nuts Diagnostic work-up Treatment Research studies and FAQs Prevalence ~4% - Peanuts – 3 million allergic in U.S. (~1.1%) Branum 2009 Pediatrics 124:1549-55 Most common cause of visits for pediatric anaphylaxis treated in U.S. Emergency Rooms > 15% of patients/year have accidental reactions Yu 2006 J Allergy Clinical Immunology 118: 466-472 100-150 deaths/year reported from food allergies - Bock SA J Allergy Clinical Immunology 2001: 107 (1): 191-193 Food culprits (n=79) . Peanut 56% . Tree nut 24% . Fish/shellfish 8% . Milk 9% . Wheat 1% . Unknown 3% Mixed nuts, baked goods, cookies, candies, Ethnic food, buffets, sauces, cross-contamination Bock S.A. AAAAI meeting 2009 . Adolescents . Nut Allergy . Known food allergy . History of Anaphylaxis . Asthma, especially those with poor control . Lack of skin symptoms . Denial of symptoms . Concomitant intake of alcohol (which may increase absorption of food) . Belief that antihistamines alone were sufficient to treat symptoms . Delay or lack of administration of epinephrine . However even timely injections of epinephrine do not necessarily prevent death (4 of 32 cases) Bock SA J Allergy Clinical Immunology 2001: 107 (1): 191-193 Can occur in 30-60 minutes Due to upper or lower respiratory compromise or cardiovascular collapse . Pumphrey et al. Clin Exp Allergy 30 (2000): 1144–1150. Adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. National Institute of Allergy and Infectious Diseases (NIAID ) Guidelines for the Diagnosis and Management of Food Allergy 2010 National Institute of Allergy and Infectious Diseases (NIAID ) Guidelines for the Diagnosis and Management of Food Allergy 2010 Signs and symptoms Percentage of cases Cutaneous >90 Urticaria and angioedema 85–90 Flush 45–55 Pruritus without rash 2–5 Respiratory 40–60 Dyspnea, wheeze 45–50 Upper airway angioedema 50–60 Rhinitis 15–20 Dizziness, syncope, 30–35 hypotension Abdominal Nausea, vomiting, 25–30 diarrhea, cramping pain Miscellaneous Headache 5–8 Substernal pain 4–6 Seizure 1–2 Over 170 foods have been reported to cause IgE-mediated reactions However over 90% of food allergies are caused by the following foods . Milk . Hen’s egg . Soy . Wheat . Peanut . Tree Nuts . Shellfish . Fish National Institute of Allergy and Infectious Diseases (NIAID ) Guidelines for the Diagnosis and Management of Food Allergy 2010 Children with food allergy*: . 35-71% atopic dermatitis ▪ Possible that peanut sensitization is associated with atopic dermatitis, use of peanut oil containing skin preparations, and household consumption of peanut** . 33-40% allergic rhinitis . 34-39% asthma * Sicherer et al. J of Allergy and Clin Immunology 2001: 108: 128-32 ** Fox et al. J of Allergy and Clin Immunology 2009: 123 (2): 417-23. Oral pruritus, rapid onset, IgE-mediated, rarely progressive Usually fresh fruits and vegetables Heat labile: cooked forms, no reaction Cause: cross reactive proteins pollen/food Birch Apple, apricot, carrot, cherry, kiwi, plum Ragweed Banana, cucumber, melon, watermelon Grass Cherry, peach, potato, tomato Pollen Foods Enterocolitis Enteropathy Proctitis Age Onset: Infant Infant/Toddler Newborn Duration: 12-24 mo 12-24 mo 9 mo-12 mo Characteristics: Failure to thrive Malabsorption Bloody stools Shock Villous atrophy Lethargy Eosinophilic Diarrhea Self limited Vomiting Non-IgE-mediated, typically milk and soy induced Spectrum may include colic, constipation and occult GI blood loss Celiac Disease (Gluten-sensitive enteropathy) . Anti-gliadin IgG, anti-endomysial IgG, IgA . Villus atrophy, malabsorption, pain, associated CA Eosinophilic esophagitis, gastritis, gastroenteritis . Eosinophilic infiltration . Poor growth, pain, vomit, diarrhea, reflux . Multiple food allergy, IgE and non-IgE-mediated . May affect varying regions of gut Gastrointestinal Anaphylaxis . Acute vomit/diarrhea, IgE-mediated Migraines Behavioral / Developmental disorders Arthritis Seizures Inflammatory bowel disease What is not a food allergy? Condition Symptoms Mechanism Bloating, abdominal pain, diarrhea Lactose intolerance Lactase deficiency (dose-dependent) Bloating, abdominal pain, diarrhea Fructose intolerance Fructase deficiency (dose-dependent) Pancreatic Malabsorption Deficiency of pancreatic enzymes insufficiency Gallbladder/liver Malabsorption Deficiency of liver enzymes disease Pain, fever, nausea, emesis, Food poisoning Bacterial toxins in food diarrhea Scombroid fish Flushing, angioedema, hives, In spoiled fish histidine is metabolized to poisoning abdominal pain histamine Pharmacologic effects of caffeine in susceptible Caffeine Tremors, cramps, diarrhea individuals Pharmacologic effects of tyramine in susceptible Tyramine Migraine individuals Auriculotemporal Facial flush in trigeminal nerve Neurogenic reflex, frequently associated with syndrome (Frey distribution associated with birth trauma to trigeminal nerve (forceps syndrome) spicy foods delivery) Profuse watery rhinorrhea Gustatory rhinitis Neurogenic reflex associated with spicy foods Subjective reactions, fainting upon Panic disorder Psychologic smelling or seeing the food Most children will outgrow cow’s milk, egg, and wheat allergy Far fewer will outgrow peanut and tree nut allergy A high initial specific IgE against the food is associated with a lower rate of resolution of clinical allergy over time Atopic dermatitis resolution is a useful marker for onset of tolerance to food allergens Skin tests to a food can remain positive long after tolerance to a food has developed. Nevertheless, reduction in the size of the skin test wheal may be a marker for the onset of tolerance to the food allergen. National Institute of Allergy and Infectious Diseases (NIAID ) Guidelines for the Diagnosis and Management of Food Allergy 2010 First foreign protein introduced into infant’s diet Most common food allergy in young children . 2.5% of children in first two years of life . 1.1% is IgE-mediated Minimal threshold dose to cause allergic reaction as low as 0.02 mL of milk (e.g. drops) Cross-reactivity with cows, goat, and sheep milk secondary to homology between these proteins . 90% children allergic to cow’s milk will be reactive to goat’s milk on oral food challenge 75% of cow’s milk allergic children will tolerate extensively heated cow’s milk (e.g. baked goods) 1-2% children Yolk considered less allergenic than white Egg white has 23 glycoproteins 70% egg allergic children may be able to ingest small amounts of egg protein in extensively heated (baked) products 0.4% children Belongs to legume family with peanut . 88% have concomitant peanut allergy 1.1% Most common food allergy in pediatric population beyond 4 years of age Most likely to cause fatalities 21.5% chance of outgrowing peanut allergy 8% risk of recurrence 0.6% population allergic Walnuts – 34% Cashews – 20% Almonds – 15% Pecan – 9% Pistachio – 7% Hazelnut, Brazil nut, Pine Nut, Macadamia nut < 5% In recent study, 12% patients allergic to more than 1 tree nut Approximately 30-50% of peanut allergic patients have at least one tree nut allergy Approximately 9% outgrow tree nut allergy . Note 14/19 patients who never ingested tree nuts but had elevated specific IgE passed the oral food challenge . Of these 14 patients, 58% with specific IgE ≤ 5 passed the