Diagnostic Techniques For Food Allergy Treatment George F

Diagnostic Techniques For Food Allergy Treatment George F. Kroker, MD FACAAI

Types of Food Reactions § Toxic Reactions § Food Intolerance § Ig. E mediated § Non Ig. E mediated (type III or IV) § Combined Ig. E and cell mediated Copyright 2015 Allergy Associates of La Crosse

Ig. E Mediated Food Allergy— Diagnostic Tools § Skin Prick Testing (SPT) § In Vitro Testing Copyright 2015 Allergy Associates of La Crosse

Skin Prick Testing for Foods § More sensitive, less specific § SPT 100% sensitive in anaphylactic range § PPV only 40 -50% in usual cases § Predictive value : wheal 8 mm > neg ctrl § More reliable in children than adults § More reliable if done with fresh foods Copyright 2015 Allergy Associates of La Crosse

In Vitro Testing for Ig. E Food Allergy § Safer, less invasive than SPT § Reliable, especially in younger children § False negatives, 10% or less ¨ (Niggermann B) § Total/specific Ig. E very high in AD, so clinical correlation advised § Specific Ig. E cutoff values established with 95% PPV anaphylaxis Copyright 2015 Allergy Associates of La Crosse

In Vitro Test: Typical Pt Screen “Maximum yield—minimal cost” § Total Ig. E § “Common Food” panel: eggs, milk, wheat, corn, § § yeast + “any food they eat a lot” and any food with a history of prior clinical reactivity, especially foods suspected of causing anaphylaxis If sensitive to specific pollens or latex, consider testing for concomitant food allergens Measure specific Ig. E to strongest clinically relevant inhalant allergen(s) by history/skin test as another “benchmark” Copyright 2015 Allergy Associates of La Crosse

In Vitro Test Interpretation: Clinical Considerations § Two allergens may have similarly positive scores, § § but differ markedly in the clinical symptoms elicited (i. e. have different “target organs”) A food allergen may have a falsely low Ig. E score if it has been avoided for a prolonged period Remember: you are measuring systemic unbound Ig. E—studies show that sometimes one may not detect systemic elevation in Ig. E yet when local mucosa is analyzed (nasally & in the gut) one may detect elevated allergen-specific Ig. E § The “x-ray” analogy Copyright 2015 Allergy Associates of La Crosse

In Vitro Test Interpretation: Clinical Considerations (Cont) § “After additional analysis, if the ELISA test results (or skin testing) remain inconsistent with the patient’s clinical history, the overriding criteria in making the final diagnosis should be the clinical history and physical examination…” Pearls and pitfalls of allergy diagnostic testing: report from the ACAAI/AAAAI Specific Ig. E Test Task Force. Cox, L et al. Annals of Allergy, Asthma and Immunology. Dec 2008; 101: 580 -592 Copyright 2015 Allergy Associates of La Crosse

ELISA Food Test—a limitation § “Measuring the whole food may not tell the whole story” § Certain components of a food may be more allergenic than others—how can we investigate this? Is it clinically relevant? Copyright 2015 Allergy Associates of La Crosse

Oral Allergy Syndrome (OAS) Copyright 2014. Allergy Associates of La Crosse

Pollen-Food Allergy Syndrome § Oral pruritus and edema, laryngeal edema, reported anaphylaxis § Ragweed pollen: melons, bananas § Birch pollen: apple, hazelnut, peaches, Copyright 2015 Allergy Associates of La Crosse

Allergen Component Diagnostic Testing § New type of allergy testing available through Thermo Fisher § www. pirllab. com § Addresses limitations of current ELISA: ¨ Current tests define allergen sources, not specific allergenic molecules Copyright 2015 Allergy Associates of La Crosse

Allergen Component Diagnostic Testing Copyright 2015 Allergy Associates of La Crosse

Panallergens of Importance § PR-10 proteins (Bet. V 1 homologue) ¨ Heat labile, causes OAS § Lipid Transfer Proteins (LTP) ¨ Heat stable, systemic reactions § Profilins ¨ Seldom cause serious clinical symptoms § Tropomyosins ¨ Cross-reactivity Copyright 2015 Allergy Associates of La Crosse shellfish, mites, cockroach

Conformational vs Linear Epitopes E G G E E G G Copyright 2015 Allergy Associates of La Crosse G G

Component Resolved Diagnosis in Food Allergy. Sadudee Boonmee, MD. Copyright 2015 Allergy Associates of La Crosse

Component Resolved Diagnosis in Food Allergy. Sadudee Boonmee MD Copyright 2015 Allergy Associates of La Crosse

Component Resolved Diagnosis in Food Allergy. Sadudee Boonmee MD Copyright 2015 Allergy Associates of La Crosse

Component Resolved Diagnosis in Food Allergy. Sadudee Boonmee MD Copyright 2015 Allergy Associates of La Crosse

Clinical Utility of Component Testing § Reveals original sensitizing source § Risk estimation for severity of reactions § Risk estimation for reaction to cooked food § Resolving cross-reactivity issues § Establishing priorities for immunotherapy Copyright 2015 Allergy Associates of La Crosse

Food Component Testing: Clinical Utility: Example #1 § “Is my child at high risk of peanut anaphylaxis with a very positive peanut ELISA test? ” § Solution—do peanut component test: § Elevated r Ara h 2 ? —yes! § Elevated r Ara h 8—no! Copyright 2015 Allergy Associates of La Crosse

Food Component Testing: Clinical Utility: Example #2 § “My child is ELISA positive to egg— what does this mean? ” § Ovomucoid -: tolerance to hardboiled egg and egg in baked goods § Ovomucoid +: confirmed egg allergy; will not tolerate any kind of egg Copyright 2015 Allergy Associates of La Crosse

Component Testing and LCM: Conclusions § Component testing may be of help in in establishing priorities in SLIT treatment ¨ Assessment may direct treatment priority in a patient with multiple fruit sensitivities ¨ Example: a patient with birch pollen allergy and OAS symptoms from apple, peach, cherries could benefit from aggressive treatment of birch allergen if Bet v 1 positive on testing Copyright 2015 Allergy Associates of La Crosse

The Mystery of Delayed Food Reactions The most beautiful thing we can experience is the mysterious. It is the source of all true Art and Science --Albert Einstein Copyright 2015 Allergy Associates of La Crosse

Immediate vs. delayed food reactions Ig. E mediated Non-Ig. E, delayed onset Patient population Pediatric predominant Adult predominant Symptom onset Minutes, hours 18 -36 hours Types of symptoms Urticaria, wheezing, congestion etc. Fatigue, myalgia, CNS, IBS, Headache, etc. Often identified by pt Yes No Standard Lab test Yes (Ig. E) No Well documented in medical literature Yes No Copyright 2015 Allergy Associates of La Crosse

Delayed-Onset Food Sensitivity Clues § Pts often present with a diagnosis of chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, migraine § Patient may have “cravings” for certain foods, and eat them excessively § Unexpected dietary changes may result in unexpected changes in baseline symptoms Copyright 2015 Allergy Associates of La Crosse

Delayed-Onset Food Sensitivity Case Examples (Cont. ) § Patient tries a high protein diet for weight loss and feels “wonderful” § Patient travels overseas and headaches go away § Patient visits sister and in 3 days her fibromyalgia “disappears” § Colonoscopy prep makes symptoms disappear Copyright 2015 Allergy Associates of La Crosse

Delayed-Onset Food Sensitivity “Clinical Pearls” § May play a role in IBS, CFS, fibromyalgia § Delayed food allergy often co-exists with delayed inhalant allergy § Patients often sick “the day after…” § Cravings for a food often present; sugar cravings suggest Candida Copyright 2015 Allergy Associates of La Crosse

Delayed-Onset Food Sensitivity “Clinical Pearls” § Multiple delayed food allergies often signal heightened intestinal permeability (i. e, “leaky gut”) § Rapid weight gain and loss suggests fluctuating edema from delayed onset food allergies § Gluten and Candida can cross-react due to “molecular mimicry” Copyright 2015 Allergy Associates of La Crosse

Delayed-Onset Food Sensitivity: The Problems § “A bad illness in search of a good test” § Usually standard Ig. E tests are negative; no widely accepted test avail § Paucity of scientific studies on tests to reliably determine diagnosis § Lack of interest by allergy profession Copyright 2015 Allergy Associates of La Crosse

Delayed-Onset Food Sensitivity Commercial Tests § Ig. G ELISA ¨ http: //www. gdx. net/product/10145 § ALCAT ¨ https: //www. alcat. com/ § Mediator Release Test (MRT) ¨ http: //nowleap. com/mediator-release-testing/mrt-iii/ Copyright 2015 Allergy Associates of La Crosse

Delayed Food Sensitivity Testing § There is no uniformly accepted in-vitro test for Delayed Food Sensitivity § The gold standard remains a rigorous trial of an elimination diet, followed by challenge Copyright 2015 Allergy Associates of La Crosse

Ig. G ELISA Test § Food-specific Ig. G may be either protective or pathologic § Principle of testing is the same as measuring Ig. E but using Ig. G instead § Multiple labs provide test—Genova Diagnostics, Meridian Valley, etc. § May have more inter-lab reproducibility than cell-based assays Reproducibility and Reliability of Two Food Allergy Testing Methods. Hodsdon, et al. Natural Medicine Journal, March 2010. Copyright 2015 Allergy Associates of La Crosse

Ig. G Food Antibody Studies § Randomized controlled trial of food elimination diet based on Ig. G antibodies for the prevention of migraine like headaches ¨ Mitchell N et al. Nutr J 3022 Aug 11; 10: 85 § Variable food-specific Ig. G antibody levels in healthy and symptomatic Chinese Adults ¨ Zeng et. Al Plos one 8(1) e 53612 (epub) 2013 Copyright 2015 Allergy Associates of La Crosse

Ig. G Food Antibody Studies § Diet restriction in migraine, based on Ig. G against foods: a clinical double-blind randomized cross-over trial ¨ Alpay K et al. Cephalgia (7): 829 -37. 2010 § The value of eliminating foods according to food-specific immunoglobulin G antibodies in irritable bowel syndrome with diarrhea ¨ Guo H et al. J Int Med Res 40(1): 204 -210, 2012 Copyright 2015 Allergy Associates of La Crosse

ALCAT Test The ALCAT test: An Evaluation of Efficacy and Clinical Applicability. Andrea Martinson Copyright 2015 Allergy Associates of La Crosse

Mediator Release Test Copyright 2015 Allergy Associates of La Crosse

Delayed Food Allergy Tests: Problems § Specificity, sensitivity, reproducibility not universally validated § False positives occur frequently, especially at levels of low reactivity § False negatives occur: ¨ Food previously avoided ¨ Food reaction non-immunologic Copyright 2015 Allergy Associates of La Crosse

Delayed-Onset Food Sensitivity Implementation of Test Results § Commercial tests serve as only an initial screening tool for clinical interpretation and diet design § “Gold standard” for diagnosing is an elimination/challenge diet § Never put pt on open-ended long term diet based on these blood tests Copyright 2015 Allergy Associates of La Crosse

Diagnostic Testing Summary Copyright 2015 Allergy Associates of La Crosse

One Final Thought… § “In the diagnosis of food allergy and food sensitivity, the best tool available to the practicing allergist is not the test results he holds in his hands, but the grey matter between his ears” Copyright 2015 Allergy Associates of La Crosse

Thank you Next: Treating Food Allergy Mary Morris MD Copyright 2015 Allergy Associates of La Crosse