The challenge of food allergies

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1 2:15 3 pm Food Allergies and Food Intolerance: Update on Guidelines Presenter Disclosure Information The following relationships exist related to this presentation: Maria Garcia-Lloret, MD: No financial relationships to disclose. SPEAKER Maria Garcia-Lloret, MD Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. What counts as a food allergy? The challenge of food allergies How prevalent are food allergies? Maria I Garcia Lloret, MD Division of Pediatric Allergy, Immunology and Rheumatology Department of Pediatrics David Geffen School of Medicine OK, food allergies are increasing. But why? Not All Food Allergies are Created Equal FOOD ALLERGY The prevalence of food allergy in children is somewhere between 2 8% IgE Mediated Non IgE Mediated The prevalence of peanut allergy quadrupled from 1997 to 2010 Eosinophilic Esophagitis Allergic Proctocolitis Food Protein Induced Enterocolitis 30% of patients have multiple food allergies

2 The economic burden of food allergic reactions in the US WHY??? million medical encounters for food allergy/anaphylaxis EXPOSURE IN UTERO AND DURING LACTATION GENETIC PREDISPOSITION TO ATOPY COMPOSITION OF THE GUT MICROFLORA Estimated direct costs indirect costs 225 million 115 million MEDICATIONS (ANTIBIOTICS, ANTIACIDS) FOOD ALLERGY CROSS-REACTIVE ANTIGENS Patel et al JACI July 2011 AMOUNT AND TIMING OF INTRODUCTION OF THE FOOD PROCESSING OF THE FOOD NON-ORAL EXPOSURE Functional composition of the gut microbiome strongly affects the health of the host The Hygiene Hypothesis Revisited Early colonization is critical for directing neonatal intestinal and immune development Multiple studies have shown that farm living is associated with less incidence of atopic disease Germ free mice have reduced number of IgA producing plasma cells skewed T cell populations, and impaired tolerance to food allergens Farm Control Commensal bacteria are involved in the breakdown and absorption of nutrients, the production of vitamins and hormones and the prevention of colonization by pathogens Differences in gut microbiota influence the absorption, bioavailability and metabolism of drugs Infants from farming mothers display a distinctive signature of innate and adaptive immune activation Asthma Atopy Etc., etc., etc. Challenging the recommendations 2000 Milk 12 mo Egg 24 mo Peanut 36 mo 2008 No evidence supporting the 2000 recommendations: limbo Learning About Peanut Allergy (LEAP) Study Randomized, open label controlled study conducted in a single site in the UK 640 babies ages 4 11 months at high risk for peanut allergy ( severe eczema, egg allergy or both ) All infants were skin tested for peanut and most underwent an oral food challenge (OFC) with peanut Babies with large (> 4mm) positive skin test to peanut or babies that reacted to peanut consumption at the baseline OFC were excluded 2015 Proof that early introduction of peanut decreases the incidence of peanut allergy Two cohorts: 1) negative skin test ( not sensitized ) 2) positive skin test (sensitized)

3 About half of infants in each cohort were randomized to either consume 6 grams of peanut protein per week or avoid all peanut Children were followed for a period of 60 months at the end of which they all underwent an OFC with 5 grams of peanut ( single dose ) What happened? Children avoiding peanut had larger skin tests and higher IgE against peanut than those eating this food regularly 86% reduction in the prevalence of peanut allergy in the active group Early, sustained consumption of peanut products is associated with a substantial and significant decrease in the development of peanut allergy in high risk infants Food Allergy : Diagnosis Trying aspects of food allergy diagnosis Financial and social challenges faced by food allergic patients Present and future therapeutic options 20% 10% Clinical history Laboratory tests Food challenge 70% Food allergies: Clinical presentation Food allergy: Testing is useful Signs and symptoms Timing of the reaction in relation to ingestion Type of food Prior exposure >80% patients have skin manifestations: flushing, urticaria, angioedema Respiratory symptoms such as nasal congestion and rhinorrhea not unusual Gastrointestinal complaints also frequent, but may be delayed Who should be tested? All individuals with a suspected food hypersensitivity. When? At the time of the initial presentation Why? To institute appropriate dietary and pharmacological management To avoid unnecessary dietary restrictions

4 Skin test Blood test The Oral Food Challenge (OFC) Inexpensive Easy to perform Immediate results Detects tissue bound IgE Not usually performed in pediatric office Somewhat subjective Affected by medications Both types of tests detect sensitization and NOT necessarily clinical reactivity Widely available to primary physicians Allows to follow trend in repeated determinations For some foods, levels indicate the risk of a systemic reaction Expensive False positives due to crossreactive epitopes False positive in patients with very elevated total IgE Gold standard for the diagnosis of food allergies Should be performed by experienced medical personnel in a controlled environment Should follow standardized protocols High degree of patient satisfaction and improvement in quality of life Promising new diagnostic modalities Food group Avoiding on admission OFC positive result OFC negative result % Negative Egg % Fruits % Milk % Peanut % Shellfish % Soy % Tree nuts % Wheat % Totals % More than 2/3 of patients with presumed clinical food allergy who undergo an oral food challenge do not react to the food. Component Resolved Diagnostics (CRD) Measures the levels of IgE against discrete peanut protein allergens, some of which are highly associated with clinical reactivity Basophil Activation Test (BAT) Flow cytometry based test where the reaction of basophils to peanut allergens is assessed in a test tube Standard of Care for Food Allergic Patients A few words on the auto injectors The recommendation AVOIDANCE Anaphylaxis action plan Epinephrine auto injector The challenge Food labelling Hidden sources Accidental exposures Recognition Access to medical care When and how Cost Underprescribed Underutilized Inadequate dosing Inadequate format Unfriendly format

5 Standard of Care for Food Allergic Patients: Special considerations General belief that certain vaccines are contraindicated in egg allergic patients but this is not supported by large epidemiological studies Per current CDC guidelines MMR is safe for all patients with a history of egg allergy Influenza vaccines also considered safe in egg allergic patients. CDC current recommendations make an exception for those patients that react to egg in all forms and have a history of anaphylaxis to this food Options for patients with severe egg allergy Flublock ( RIV3, recombinant, egg free) in patients older than 18 years old. For younger patients or if Flublock not available administer IIV in clinic if comfortable recognizing and managing systemic allergic reactions. Monitor for 30 min Flumist not recommended AND SPEAKING OF ANAPHYLAXIS CLINICAL CRITERIA FOR ANAPHYLAXIS Acute onset (minutes to hours) DEFINITION Serious allergic reaction that is rapid in onset and may cause death. Skin and/or mucosal tissue + 1 Respiratory compromise Reduced BP,collapse, syncope Exposure to a likely allergen +2 Skin/mucosal signs Respiratory compromise Reduced BP,collapse Persistent GI symptoms I KNOW IT WHEN I SEE IT Exposure to a known allergen Low systolic BP Management of Anaphylaxis A few other aspects to bear in mind Patient recumbent with elevated extremities Epinephrine x1 or more q 5 15 minutes Beta Agonists Fluid Resuscitation Antihistamines (H1 and H2) Glucocorticoids Methylene Blue High parental and patient anxiety Limited family activities Social isolation Bullying School absenteeism

6 What is allergen immunotherapy (AIT)? AIT Administration of gradually increasing doses of allergen that modify the immune response in a way that decreases clinical reactivity. Desensitization Tolerance It is the only available treatment capable of modifying the course of allergic disease. Transient increase in the threshold of clinical reactivity. Effect lost upon discontinuation Permanent change in the immune response resulting in long lasting protection irrespective of ongoing exposure AIT Routes of Administration Rush desensitization Days Subcutaneous Oral (OIT) Sublingual (SLIT) Build up Maintenance Weeks to months Months to years Epicutaneous (EPIT) Intralymphatic Efficacy is assessed by OFC while on treatment (desensitization) and while off therapy (tolerance ) 50+ clinical trials assessing the efficacy of OIT for food allergy Reported outcomes promising for egg and peanut, showing favorable response in about 50% of patients Many children with an initial favorable response regained their clinical reactivity a few months after discontinuing therapy Too soon to tell if this form of OIT can promote tolerance % Responders VIPES study: Easing the concern about accidental exposures and more Placebo Peanut 250 DBPC 221 peanut allergic patients Patch with 50,100 or 250 mcg of peanut protein Daily application over 12 mo Children ( 6 11) in the active arm were on average able to consume 1000 mg of peanut protein or at least 10 fold more than at baseline Favorable immunological changes: Decrease in IgE, increase in IgG4

7 TAKE HOME POINTS Early introduction of peanut ( and possibly other common food allergens) reduces the risk of peanut allergy later in life. High risk infants ( eczema, other food allergies ) MUST be evaluated/tested by an allergist prior to the introduction of highly allergenic foods Food challenges are the gold standard at the time of diagnosing a true food allergy and should be recommended more often TAKE HOME POINTS OIT is feasible but at present not recommended outside the clinical research setting EPIT promising bridge therapy that increases the threshold of clinical reactivity New diagnostic modalities may better discriminate between sensitized and clinically reactive patients Case 1 8 month old infant Extensive atopic dermatitis with frequent flares Exclusively breastfed for six months Eating pureed fruits and vegetables with no problems, but developed hives after eating a small amount of egg white What next?? The Next What we know 50% babies with eczema show evidence of egg sensitization Many will react to raw or lightly cooked egg but will tolerate highly denatured egg Babies with eczema and egg sensitization are at a high risk of peanut allergy What we can do Confirm the diagnosis of egg allergy (blood test or skin test ) Consider challenge with baked egg Assess for the presence of peanut sensitization If peanut tests are negative, introduce peanut in the diet If peanut tests are positive, consider oral challenge with peanut Case 2 The Next Kindergartener What we know What we can do Extensive eczema, resolved Diagnosed with peanut allergy by a blood test at age 2 (peanut IgE 5 KU) Avoiding peanuts and tree nuts ever since Family is very worried because there are no allergen free schools in her district and they are thinking of moving to another area or home schooling What next? A positive test does not always imply clinical reactivity Up to 20% of children with peanut allergy outgrow their condition Only a third of children with peanut allergy are also allergic to tree nuts Reassess the level of peanut specific IgE If value is 20 ku or above, likely peanut allergic Consider oral challenge and inclusion in protocol of oral immunotherapy If value is 5 ku and below, do challenge with peanut Value between 5 and 20 grey zone Consider risk factors, consider peanut challenge Reassess tree nut sensitization

8 29 year old junior executive Exercise induced asthma Known lactose intolerance 1 year history of bloating, abdominal pain and fatigue with multiple other foods Symptoms have become more severe in the last two months A friend told her the problem could be gluten What next? Case 3 What we know Food intolerance usually due to incomplete or poor digestion due to an absolute or relative enzymatic deficiency. Dose dependent. Symptoms restricted to the GI tract Available tests can confirm lactose intolerance The Next Food sensitivity presumably due to an as yet undefined immune reaction. Patients report a variety of symptoms in addition to GI Overlap between IBS and food sensitivity Non celiac gluten sensitivity is a disorder gaining some acceptance in the medical community There are NO VALID tests for food sensitivities What we can do Thorough physical exam and history, including dietary history. Consider labs : nutritional assessment (Vitamin D), IgE for wheat and celiac screening. If the above are negative, consider dietary exclusion for 6 weeks DO NOT request food specific IGG or IGG4 panel ( expensive, not validated ) If symptoms dramatically improve, you may have your answer. If not, look for other etiologies. UCLA Food Allergy Program Gastroenterology Allergy Immunology Nutrition

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