Table of Contents

Cover

Table of Contents

Half title page

Title page

Copyright page

DEDICATION

PREFACE

CONTRIBUTORS

GLOSSARY OF TERMS

Part I: FOOD ALLERGY AND THE CONSUMER

1 IMMUNE-MEDIATED ADVERSE REACTIONS TO DIETARY PROTEINS

1.1. INTRODUCTION

1.2. ORAL IMMUNE TOLERANCE

1.3. FOOD ALLERGY

1.4. CELIAC DISEASE (CD) AND RELATED CONDITIONS

1.5. CONCLUSIONS

ACKNOWLEDGMENTS

2 PROTECTING FOOD-ALLERGIC CONSUMERS: MANAGING ALLERGENS ACROSS THE FOOD SUPPLY CHAIN

2.1. INTRODUCTION

2.2. LIVING WITH FOOD ALLERGIES—CHALLENGES FOR THE ALLERGIC CONSUMER

2.3. LEGISLATIVE AND REGULATORY CONSIDERATIONS

2.4. FOOD ALLERGEN TESTING WITHIN A FOOD BUSINESS CONTEXT

2.5. CONCLUSION

ACKNOWLEDGMENTS

3 CRITERIA TO DETERMINE PRIORITY ALLERGENS: TREE NUT ALLERGY REVIEW

3.1. INTRODUCTION

3.2. TREE NUT ALLERGY

3.3. CRITERIA TO DETERMINE A MAJOR FOOD ALLERGEN

3.4. CONCLUSION

ACKNOWLEDGMENT

4 THE CANADIAN CRITERIA FOR THE ESTABLISHMENT OF NEW PRIORITY FOOD ALLERGENS: EVIDENCE FOR THE INCLUSION OF MUSTARD AND INSUFFICIENT EVIDENCES FOR GARLIC AND ONION AS PRIORITY ALLERGENS IN CANADA

4.1. INTRODUCTION

4.2. CANADIAN CRITERIA FOR THE ESTABLISHMENT OF NEW PRIORITY FOOD ALLERGENS

4.3. MUSTARD: EVIDENCE FOR ITS INCLUSION AS A PRIORITY FOOD ALLERGEN IN CANADA

4.4. GARLIC AND ONIONS: INSUFFICIENT EVIDENCE TO BE INCLUDED ON THE LIST OF PRIORITY FOOD ALLERGENS IN CANADA

4.5. SUMMARY

ACKNOWLEDGMENTS

Part II: GENERAL PRINCIPLES FOR ALLERGEN MANAGEMENT AND CONTROL

5 ALLERGEN MANAGEMENT AND CONTROL AS PART OF AGRICULTURAL PRACTICES

5.1. ALLERGEN MANAGEMENT AND CONTROL AS PART OF AGRICULTURAL PRACTICES

5.2. PRECAUTIONARY PROCEDURES TO AVOID CONTAMINATION

5.3. NEW DEVELOPMENTS IN ALLERGEN MANAGEMENT FOR SPECIFIC GRAINS (E.G., OATS)

6 PRINCIPLES AND PRACTICES FOR ALLERGEN MANAGEMENT AND CONTROL IN PROCESSING

6.1. INTRODUCTION

6.2. MANAGEMENT RESPONSIBILITIES

6.3. PROGRAMS DESIGNED TO PREVENT CROSS-CONTACT

6.4. ALLERGEN CONTROL AND PRODUCT DEVELOPMENT

6.5. CONCLUSION

7 ALLERGEN MANAGEMENT AND CONTROL IN THE FOODSERVICE INDUSTRY

7.1. BIOGRAPHY

7.2. INTRODUCTION

7.3. BACKGROUND

7.4. FOOD PREPARED BY STRANGERS

7.5. THE ADVENT OF DIETARY NEEDS—SPECIAL OR NOT

7.6. SIGNS OF THE TIMES

7.7. WHICH ALLERGENS?

7.8. WHAT DO WE KNOW ABOUT THOSE AT RISK?

7.9. EFFECTIVE AVOIDANCE

7.10. UNRECOGNIZED INGREDIENTS

7.11. EFFECTIVE ALLERGEN AVOIDANCE IN DIFFERENT ENVIRONMENTS

7.12. FOOD ALLERGY IN CONTEXT

7.13. WHAT WORKS IN FOODSERVICE?

7.14. FOOD ALLERGY AND THE LAW

7.15. BEST PRACTICE GUIDANCE

7.16. CONCLUSION

ACKNOWLEDGMENTS

Part III: PROCESSING FOODS FREE FROM SPECIFIC ALLERGENS

8 PROCESSING FOODS FREE FROM DAIRY PROTEINS

8.1. INTRODUCTION

8.2. OVERVIEW OF DAIRY INGREDIENTS, THEIR PROCESSING, AND CHARACTERISTICS

8.3. MILK PROTEIN ALLERGENS

8.4. EFFECTS OF PROCESSING ON DAIRY ALLERGENS

8.5. NUTRITIONAL AND FUNCTIONAL ALTERNATIVES TO DAIRY INGREDIENTS

8.6. CROSS-REACTIVITY

8.7. CONCLUSION

9 PROCESSING OF EGG-FREE FOODS

9.1. INTRODUCTION

9.2. GENERALITIES ON EGG AND EGG ALLERGY

9.3. EGG: A MULTIFUNCTIONAL INGREDIENT IN THE FOOD INDUSTRY

9.4. MANAGING THE ALLERGEN RISK TO PRODUCE EGG-FREE FOODS

9.5. CONCLUSIONS

10 FISH AND SHELLFISH ALLERGENS

10.1. INTRODUCTION

10.2. FISH AND SHELLFISH ALLERGY

10.3. FOOD PRODUCTS CONTAINING FISH AND FISH INGREDIENTS

10.4. EFFECTS OF PROCESSING ON ALLERGENICITY

10.5. CONCLUDING REMARKS

11 PROCESSING FOODS WITHOUT PEANUTS AND TREE NUTS

11.1. INTRODUCTION

11.2. PEANUT AND TREE NUT ALLERGY

11.3. NUTRITIONAL AND FUNCTIONAL PROPERTIES OF PEANUTS AND TREE NUTS

11.4. NUTRITIONAL AND FUNCTIONAL ALTERNATIVES TO PEANUTS AND TREE NUTS

11.5. HIDDEN AND UNINTENTIONAL SOURCES OF PEANUT AND TREE NUT ALLERGENS

11.6. ANALYTICAL TOOLS FOR DETECTION OF PEANUT AND TREE NUT ALLERGENS

11.7. GUIDELINES FOR PROCESSING FOODS “FREE FROM” PEANUTS AND TREE NUTS

11.8. CONCLUSION

12 PROCESSING GLUTEN-FREE FOODS

12.1. INTRODUCTION

12.2. OVERVIEW OF AVAILABLE GLUTEN INGREDIENTS AND TERMINOLOGIES

12.3. IDENTIFYING NUTRITIONAL AND FUNCTIONAL ALTERNATIVES TO WHEAT, BARLEY, AND RYE

12.4. HIDDEN AND UNINTENTIONAL SOURCES OF GLUTEN

12.5. GUIDELINES FOR GLUTEN-FREE PROCESSING

12.6. CONCLUSION

13 PROCESSING FOODS WITHOUT SOYBEAN INGREDIENTS

13.1. INTRODUCTION

13.2. COMPOSITION AND MOLECULAR PROPERTIES OF SOYBEAN AND SOYBEAN COMPONENTS

13.3. ALLERGENICITY OF SOYBEAN

13.4. TECHNIQUES TO REMOVE OR REDUCE THE ALLERGENICITY OF SOYBEAN PROTEINS

13.5. IDENTIFYING REPLACEMENTS FOR SOYBEAN AND SOY PRODUCTS IN DIFFERENT FOOD APPLICATIONS

13.6. HIDDEN AND UNINTENTIONAL SOURCES OF SOYBEAN AND SOY PRODUCTS IN FOOD PROCESSING

13.7. SOYBEAN CROSS-REACTING ALLERGENS

13.8. IMPORTANCE OF GOOD MANUFACTURING PRACTICES (GMPs)

13.9. CONCLUSION

14 MANUFACTURING A BISCUIT THAT DOES NOT USE MILK, EGGS, OR SOYBEANS

14.1. INTRODUCTION

14.2. ALLERGEN MANAGEMENT INITIATIVE

14.3. ALLERGEN MANAGEMENT OF THE AMARANTH BISCUIT

14.4. MILK AND EGG ANALYSIS

14.5. CONCLUSION

Part IV: RISK ASSESSMENT AND RISK MANAGEMENT

15 RISK ASSESSMENT FOR FOOD ALLERGY

15.1. INTRODUCTION

15.2. RISK ASSESSMENT

15.3. CHALLENGES AND LIMITATIONS IN THE ESTABLISHMENT OF MEDS (THRESHOLDS)

15.4. MOLECULAR, TECHNOLOGICAL, AND PROCESSING CHALLENGES: ASSESSING THE ALLERGENIC RISK FROM FOOD TREATMENTS AND MODIFICATIONS

15.5. FOODS WITH REDUCED ALLERGENICITY: THE ROLE OF RISK ASSESSMENT

15.6. CHALLENGES WITH ALLERGEN DETECTION TOOLS

15.7. CHALLENGES AND LIMITATIONS IN DETERMINING ALLERGEN EXPOSURE FOR RISK ASSESSMENT

15.8. LIMITATIONS OF EXISTING ALLERGEN MANAGEMENT PROGRAMS

15.9. CONCLUSIONS

16 THE CHALLENGES OF PRECAUTIONARY LABELING

16.1. INTRODUCTION

16.2. PRECAUTIONARY LABELING

16.3. THE CHALLENGES ASSOCIATED WITH PRECAUTIONARY LABELING

16.4. EVOLVING A BETTER SYSTEM FOR PRECAUTIONARY LABELING

16.5. VITAL: THE AUSTRALIAN RESPONSE TO THE CHALLENGES OF PRECAUTIONARY LABELING

16.6. CONTINUOUS IMPROVEMENT

17 CERTIFICATION PROGRAMS FOR FOODS LABELED AS “FREE FROM” SPECIFIC ALLERGENS

17.1. INTRODUCTION TO THE CERTIFICATION PROCESS

17.2. STEPS IN THE CERTIFICATION PROCESS

17.3. ENSURING THAT CERTIFIED ALLERGEN-FREE PRODUCTS REMAIN COMPLIANT

17.4. BUSINESS RESPONSE TO NONCOMPLIANCES IDENTIFIED BY THE CERTIFICATION AGENCY

17.5. TPC AND HOW TO MAINTAIN AND CONTINUE ALLERGEN-FREE CERTIFICATION

17.6. KEY POINTS TO CONSIDER IN SETTING UP A CERTIFICATION PROGRAM (SPONSORING ORGANIZATION)

17.7. DOCUMENTATION

17.8. CONCLUSION

18 EMERGING ALLERGENS AND THE FUTURE

18.1. OVERVIEW OF MAJOR FOOD ALLERGENS

18.2. MINOR AND EMERGING ALLERGENS

18.3. PREVALENCE AND INCIDENCE

18.4. POTENTIAL IMPACT ON THE FOOD INDUSTRY AND FOR THE CONSUMERS

18.5. CONCLUSION

18.6. USEFUL WEBSITES FOR INFORMATION ON FOOD ALLERGY

19 MANAGING RISKS AND PREVENTING FOOD ALLERGY INCIDENTS: A REGULATOR’S PERSPECTIVE

19.1. INTRODUCTION

19.2. IMPACTS AND RATIONALE FOR ACTION TO PREVENT FOOD ALLERGY INCIDENTS

19.3. RISK MANAGEMENT OPTIONS TO PREVENT AND MANAGE FOOD ALLERGY INCIDENTS

19.4. DIETARY ADVICE DURING PREGNANCY AND LACTATION

19.5. FOOD ALLERGY INCIDENT SURVEILLANCE AND REPORTING SYSTEM

19.6. CONCLUSION

Index

ALLERGEN MANAGEMENT IN THE FOOD INDUSTRY

Copyright © 2010 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New Jersey

Published simultaneously in Canada

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Library of Congress Cataloging-in-Publication Data:

Allergen management in the food industry / edited by Joyce I. Boye, Samuel Benrejeb Godefroy.

p. cm.

Includes index.

Summary: “This book comprehensively addresses the sources of allergenic contaminants in foods, their fate during processing, and the specific measures that need to be taken to minimize their occurrence in foods. The book provides up-to-date information on the nine major allergens (as well as other emerging allergens) and practical guidelines on how these allergens can be identified and controlled during production and processing. Starting with an introduction to food allergens, the book follows with sections on food allergen management during production and processing, guidelines for the processing of specific allergen-free foods, techniques for hypo-allergenization and allergen detection, and allergen-free certification”—Provided by publisher.

Summary: “This book comprehensively addresses the sources of allergenic contaminants in foods, their fate during processing, and the specific measures that need to be taken to minimize their occurrence in foods”—Provided by publisher.

ISBN 978-0-470-22735-0 (hardback); 978-1-118-06028-5 (ebk)

 1. Food allergy—Prevention. 2. Food industry and trade. I. Boye, Joyce I. I. Godefroy, Samuel Benrejeb.

RC596.A557 2010

616.97′5—dc22

2010024927

When food is your enemy, knowledge is your best weapon of defence.

Anonymous, 2009

PREFACE

Food allergic reactions have emerged as a growing challenge to the food industry. The statistics are quite remarkable: ∼4–8% of children and ∼2–4% of the adult population are believed to have food allergies. Allergic reactions are particularly bothersome because in some unfortunate situations, they have resulted in anaphylaxis and even death. For example, the death of a young girl in Ontario, the most populated province in Canada, after consumption of french fries that had been inadvertently in contact with a dairy product in her school cafeteria resulted in increased awareness about food allergies, leading legislators in the province to enact what is now known as Sabrina’s law. This legislation requires schools in Ontario to be proactive about allergy education and preparedness. The death of Sabrina is not unique, and unfortunately, other incidents have occurred around the world. Of the over 160–180 foods known to be allergenic, some are considered priority allergens. These include eggs, milk, soy, peanuts, tree nuts, fish, shellfish, and wheat (gluten). The health burden of allergies and allergy-related diseases still remains unclear.

To protect food-allergic consumers, several countries around the world have put in place food allergen labeling regulations requiring food industries to label the priority allergens when they are present in foods. This has posed some challenges to the food industry and has resulted in discussions on the need of allergen management programs to allow the identification of allergens in the food supply chain and their avoidance in foods targeted toward food-allergic consumers. The objective of food safety regulators and the food industry, ultimately, is to provide safe foods to allergic consumers and their families while maximizing choice.

The market for allergen-free foods has grown astronomically as the food industry has awakened to the potential for growth of this sector. These developments are exciting and provide a glimmer of hope in a world that has proven to be hazardous for allergic individuals. The eagerness of the food industry to embrace this market and the readiness of regulatory agencies to provide guidelines to support the sector is palpable. It is in this context that this book has been compiled, which focuses on providing practical and timely information on the manufacturing of foods targeted for allergic consumers. Renowned experts from around the world working in the area of food allergy have contributed excellent reviews covering the spectrum of allergen management from “farm to fork.” The target audience for the proposed book includes food scientists and food processors in academia (professors, researchers, students) and the food industry. The book’s comprehensive nature will also appeal to scientists and researchers in general involved in allergy research, food inspection, food safety certification, and policy making.

The book is divided into four parts. Part I begins with Chapter 1, which provides an overview of food allergy and food intolerance and the mechanisms involved in sensitization and elicitation. A clear distinction between food allergy and food intolerance is provided as well as a definition of gluten hypersensitivity. Chapters 2, 3, and 4 provide a summary of the major issues that need to be addressed in allergen management and the criteria for determining priority allergens, using tree nuts and mustard as an example.

Part II contains three chapters that address, respectively, allergen management in agricultural practices (on the farm), food processing, and the foodservice industry.

In Part III, Chapters 8–13, respectively, provide in-depth reviews of each of the following priority allergens: dairy, eggs, fish and crustaceans, peanuts and tree nuts, gluten, and soy. Critical information is provided for the processing of foods targeted for consumers suffering from theses specific allergies. Chapter 14, the last chapter in this part, provides a practical example of a food product formulated to be “free from” milk, eggs, and soybeans.

Chapters 15–17 of Part IV, address, respectively, allergen risk assessment and risk management, precautionary labeling, and allergen-free certification. As more “allergen-free” products are introduced into the market, consumers, as well as the food industry, need to consider the risks and benefits of auto-certification versus third-party certification. Chapter 18 discusses in detail some of the emerging allergens (e.g., lupin, sesame, and mustard) and their properties and the need to monitor these foods as global movement and trade exposes consumers to an ever-increasing array of new and novel foods. The last chapter, Chapter 19, provides practical tools for managing food allergen risks.

One of the important areas of food allergy requiring further investigation is the threshold dose required to provoke allergic reactions. Zero tolerance, while desirable, poses serious challenges to the food industry and could increase processing costs considerably. Knowledge of the amount of allergens required to elicit allergic reactions may help to provide realistic targets for the industry. While this subject is beyond the scope of this book, results of current studies such as those being conducted by the European Union Network (EuroPREVALL, http://www.europrevall.org) should shed more light on this important area. Methods for allergen detection are not addressed in this book, as they have been effectively discussed in the book Detecting Allergens in Food (edited by S.J. Koppelman and S.L. Hefle, CRC Press and Woodhead Publishing, 2006). There continues to be a need, however, for improved methods for allergen detection that take into consideration the effect of processing and matrix.

The reader will sometimes find the use of multiple terminologies in the text and different statistics for allergy prevalence rates. This is expected in a field that is transitioning from infancy into adolescence. An example that requires mentioning is the use of the terms “cross-contact” and “cross-contamination.” As “cross-contamination” has been traditionally used in the food safety context to refer to contamination by pathogenic microorganisms, “cross-contact” has evolved as a more adequate terminology to describe the inadvertent presence of allergenic substances in the food chain. These two terms are used interchangeably throughout the book. Additionally, various numbers have been reported in the literature for allergy prevalence rates, ranging from 4% to 8% for children and 1% to 4% of the adult population. This variability is reflected in some of the literature cited in the text.

We would also like to mention that while effort has been made to minimize duplication, in a volume that attempts to cover a spectrum as large as this, some repetition is unavoidable. There may also be some errors in the text especially in a field such as this one, which is quickly evolving. We take responsibility for any such errors and would kindly request that readers inform us of any such errors so appropriate corrections and additions can be made in any future editions. Finally, we would like to thank the contributors for doing such a stellar job of compiling the most up-to-date information for the management of food allergens. It is a remarkable piece of work, and we sincerely thank them for their hard work and dedication.

JOYCE I. BOYE

SAMUEL BENREJEB GODEFROY

CONTRIBUTORS

Allaoua Achouri, Food Research and Development Centre, Agriculture and Agri-Food Canada, Saint-Hyacinthe, Quebec, Canada

Anton J. Alldrick, BRI Campden, Chipping Campden, UK

Elke K. Arendt, Department of Food and Nutritional Sciences, University College Cork, Ireland

Joyce I. Boye, Food Research and Development Centre, Agriculture and Agri-Food Canada, Saint-Hyacinthe, Quebec, Canada, J2S 8E3; Email: joyce.boye@agr.gc.ca

Michel Britten, Food Research and Development Centre, Agriculture and Agri-Food Canada, 3600 Casavant Blvd West, Saint-Hyacinthe, Quebec, Canada

Vernon D. Burrows, Eastern Cereal and Oilseed Research Centre, Agriculture and Agri-Food Canada, Central Experimental Farm, Ottawa, Ontario, Canada

René W.R. Crevel, Safety & Environmental Assurance Centre, Unilever, Sharnbrook, Bedford, UK

Angelina O. Danquah, Department of Home Science, University of Ghana, Legon, Ghana

Philippe Delahaut, CER Groupe––Laboratoire d’Hormonologie, Marloie, Belgium

Lilla Dömötör, Szx151_TimesTen-Roman_10n_000100dliget, Budapest, Hungary

Sheila Dubois, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada

Valéry Dumont, CER Groupe––Laboratoire d’Hormonologie, Marloie, Belgium

Audrey DunnGalvin, College of Medicine and Health, Department of Paediatrics and Child Health, University College Cork, Ireland

Christine Dupuis, Bureau de Normalisation du Québec (BNQ), Montreal, Quebec, Canada

Fiona Fleming, George Weston Foods, Sydney, New South Wales, Australia

Zoë Gillespie, Bureau of Chemical Safety, Food Directorate, Health Canada, Ottawa, Ontario, Canada

Samuel Benrejeb Godefroy, Food Directorate, Health Canada, Ottawa, Ontario, Canada

M. Hazel Gowland, Allergy Action, St Albans, UK

Kirsten Grinter, Nestle Australia Ltd., Sydney, New South Wales, Australia

Sandra Kerbach, Eurofins Analytik GmbH, Hamburg, Germany

Sébastien La Vieille, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada

Kim Leighton, Australian Food and Grocery Council, Canberra, Australian Capital Territory, Australia

Lamia L’Hocine, Food Research and Development Centre, Agriculture and Agri-Food Canada, Saint-Hyacinthe, Quebec, Canada

E.N. Clare Mills, Institute of Food Research, Colney, Norwich, UK

Kevin Norman, Peanut Company of Australia, Kingaroy, Queensland, Australia

Maria Helena B. Nunes, Department of Food and Nutritional Sciences, University College Cork, Ireland

Takahide Obata, Research Institute, Morinaga and Co. Ltd., Yokohama, Japan

Sylvia Pfaff, Food Information Service Europe, Bad Bentheim, Germany

Roland E. Poms, International Association for Cereal Science and Technology (ICC), Vienna, Austria

Bert Popping, Eurofins Scientific Group, Yorkshire, UK

Chris Preston, Legal Finesse, Sydney, New South Wales, Australia

Olga M. Pulido, Bureau of Food Policy and Science Integration, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada; and Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada

Sahul H. Rajamohamed, Food Research and Development Centre, Agriculture and Agri-Food Canada, Saint-Hyacinthe, Quebec, Canada

Maria Said, Anaphylaxis Australia, Sydney, New South Wales, Australia

Masahiro Shoji, Morinaga Institute of Biological Science, Inc., Yokohama, Japan

Benjamin K. Simpson, Department of Food Science and Agricultural Chemistry, Macdonald Campus, McGill University, Sainte-Anne-De-Bellevue, Quebec, Canada

Warren E. Stone, Grocery Manufacturers Association, Washington, DC

Ferdinand Tchounkeu, Québec Food Allergies Association (QFAA), St-Léonard, Montréal, Québec, Canada

Sandor Tömösközi, BUTE, Department of Applied Biotechnology and Food Science, Budapest, Hungary

Jupiter M. Yeung, Nestlé Nutrition, Nestlé Product Technology Center, Fremont, MI

GLOSSARY OF TERMS

Adaptive (acquired) immunity (specific immunity).

This is the response of the immune system to a specific immune stimulus (antigen). The immune system “remembers” that it has encountered a specific antigen and reacts more rapidly on subsequent exposure (immune surveillance). Critical to adaptive immunity are antigen-presenting cells (APCs) including macrophages and dendritic cells, antigen-dependent stimulation of T-cell subtypes, B-cell activation leading to antibody production, and the activation of macrophages and natural killer (NK) cells.

Allergen.

A substance that causes an inappropriate reaction by the immune system “an allergic reaction.”

Allergic proctocolitis.

A benign disorder manifesting with blood-streaked stools in otherwise healthy-appearing infants who are breast- or formula-fed. Its clinical features and laboratory results are often nonspecific. Symptoms resolve within 48–72 hours following elimination of dietary cow’s milk protein. The underlying mechanism is not known, though IgE is clearly not implicated. Endoscopy shows focal or diffuse colitis, with edema and erosions. The biopsy reveals eosinophilic infiltration with focal distribution.

Allergy.

A hypersensitivity reaction initiated by immunologic mechanisms.

Anaphylaxis.

A systemic IgE-mediated allergic reaction that can be fatal within minutes, by compromising the airways or through a dramatic drop in blood pressure. In a sensitized, susceptible person, contact with or ingestion of an allergen may elicit an IgE-mediated adverse immune response leading to airway obstruction, hypotension, and loss of consciousness, resulting in anaphylactic shock. In anaphylaxis, several systems are usually affected simultaneously, including the respiratory tract, cardiovascular system, and gastrointestinal tract.

Angioedema.

Refers to locally diffuse and painful soft-tissue swelling that may be asymmetric, especially on the eyelids, lips, face, and tongue, but also on the back of hands or feet and on the genitals. If angioedema affects the throat, the person’s airway could be blocked, which could be life threatening.

Antibodies (Abs).

Also called immunoglobulins (Igs) that are released by plasma cells. When a B cell encounters an antigen, it is stimulated to mature into a plasma cell or a memory B cell. Each antibody molecule has two parts. One part varies and is specialized to attach to a specific antigen. The other part is one of five structures, which determines the antibody’s class—IgM, IgG, IgA, IgE, or IgD. This part is the same within each class and determines the function of the antibody.

Antigen-presenting cells (APCs).

T-cell-dependent acquired immune responses typically require antigen-presenting cells to present Ag-derived peptides within major histocompatibility complex (MHC) molecules.

Antigens (Ag).

A substance, usually proteins or polysaccharides, capable of stimulating the immune system to produce antibodies.

Asthma.

An allergic-mediated response in the bronchial airways and a common disorder characterized by chronic inflammation of the bronchial tree with consequent reduction of airflow and symptomatic wheezing and dyspnea. Asthmatics are more responsive than nonasthmatics to a wide range of triggers capable of initiating an asthmatic episode. The narrowing of the bronchial tree (bronchi) is usually reversible, but in some patients with chronic asthma, there may be an element of irreversible airflow obstruction. Asthma involves only the bronchi and does not affect the air sacs (alveoli) or the lung parenchyma itself.

Atopic dermatitis (AD).

A pruritic, chronic inflammatory skin disease of unknown origin that usually starts in early infancy; it is characterized by eczematous lesions, dryness, and thickening of the skin. AD may be associated to acute allergic reactions to foods. Genetic factors are important in the development of AD and are often associated with a personal or family history of other atopic diseases. The association of food allergy with atopic dermatitis has been demonstrated and IgE and non-IgE cellular mechanisms have been implicated. AD is considered to be an inherited genetic disorder with an allergic diathesis.

Atopy.

A personal or familial tendency to produce IgE antibodies in response to low doses of allergens, confirmed by a positive skin prick test, and typical symptoms such as asthma, rhinoconjunctivitis, or eczema/dermatitis.

Autoimmune disorders.

Refers to medical conditions that occur when the immune system mistakenly attacks “itself” and destroys healthy body tissue. There are more than 80 different types of autoimmune disorders.

Blood pressure.

The pressure of the blood within the arteries produced primarily by the contraction of the heart muscle. Its measurement is recorded by two numbers. The first (systolic pressure) is measured after the heart contracts and is recorded by the highest number. The second (diastolic pressure) is measured before the heart contracts and is recorded by the lowest number. Elevation of blood pressure is called “hypertension.”

Bronchial asthma.

Refers to the definition of asthma.

Bronchospasm.

Spasmodic contraction of the muscular walls of the bronchial air passages as observed in asthma; it is associated with breathing difficulty.

Cardiovascular.

The heart and the blood vessels as a unified body system.

Conjunctivitis.

Inflammation of the mucous membrane lining the inner surface of the eyelids and covering the front part of the eyeball.

Cross-contact/contamination.

Refers to a food contaminating or entering in contact with another unrelated food leading to a “hidden” source of allergenic proteins.

Cross-reactivity.

The concept of cross-reactivity concerns two allergens and an antibody. The term is used to describe a relation between two allergens and a cross-reactive antibody. The closer the similarity between the two allergens, the more likely it is to find a cross-reactive antibody. A variety of cross-reacting allergens are present among foods and aeroallergens. Allergen cross-reactivity can be detected when tested in vitro, but clinical correlation of the cross-reactivity is more variable. For example, cow’s milk allergy is a common disease of infancy and childhood. Goat’s milk cross-reacts with cow’s milk. Cow’s milk allergic patients may also react to goat’s and/or sheep’s milk.

Cytokines.

Polypeptides secreted by immune and other cells when the cell interacts with a specific antigen, endotoxin, or other cytokines.

Dermatitis.

An umbrella term for local inflammation of the skin.

Diaphoresis.

Perspiration, especially when profuse.

Dyspnea.

Shortness of breath.

Eczema.

A general term for many types of skin inflammation, also known as dermatitis, and is characterized by itching and the formation of scales. It is a very common condition and can affect all races and ages, including young infants. The most common form of eczema is atopic dermatitis.

Eosinophilic esophagitis.

A primary clinicopathologic disorder of the esophagus, characterized by (1) symptoms including, but not restricted to, food impaction and dysphagia in adults, and feeding intolerance and gastroesophageal reflux disease (GERD) symptoms in children; (2) biopsy with ≥15 eosinophils/high power field; (3) exclusion of other disorders associated with similar clinical, histological, or endoscopic features, especially GERD. Appropriate treatments include dietary approaches based on eliminating exposure to food allergens, or topical corticosteroids.

Erythema.

An abnormal redness of the skin caused by various agents, as sunlight, drugs, and so on, that irritate and congest the capillaries.

Exercise-induced anaphylaxis.

Exercise can induce an allergic reaction to food. The usual scenario is that of a person eating a specific food and then exercising. As the individual exercises and their body temperature increases, they begin to itch, get lightheaded, and soon develop the characteristic allergic reactions of hives, asthma, abdominal symptoms, and even anaphylaxis. Refer to the definition of anaphylaxis or systemic reaction.

Favism.

Disease that develops in genetically predisposed individuals when they ingest broad beans or fava beans or inhale the flower pollen. The condition is a result of a deficiency of glucose-6-phosphate dehydrogenase in the red blood cells and of reduced glutathione, which is needed for red blood cell integrity. Fava beans contain substances that oxidize glutathione, which results in acute hemolytic anemia. The condition is not IgE mediated and is therefore regarded as food intolerance. Areas of the world most affected by this disease are the Mediterranean, Asia, Middle East, and Formosa. In the United States, favism is reported to affect 1–2% of Caucasian-Americans and 10–15% of African-Americans.

Flushing.

Sudden redness of the skin, especially of the head and neck.

Gastrointestinal.

Refers collectively to the stomach and small and large intestines.

Glottis.

The middle part of the larynx; the area where the vocal cords are located.

Gluten sensitivity.

This term as used in the literature is confusing and has been used to express various types of adverse reactions to dietary gluten. Gluten sensitivity enteropathy is a term used inter-changeably with celiac disease (CD). The term gluten sensitivity has also been used to encompass other autoimmune conditions associated with gluten exposure but that often present without gastrointestinal symptoms and bowel pathology, e.g., gluten ataxia and gluten neuropathy. On the other hand, emerging research has used the term gluten sensitivity to differentiate between the autoimmune enteropathy CD and those individuals who may present with symptoms similar to CD, but without anti-tTG autoantibodies or the autoimmune comorbidities (Hadjivassiliou et al. 2010; Sapone et al. 2010). The specific genetic profiles and mechanisms involved in distinguishing the different conditions associated with gluten toxicity are just beginning to be elucidated and the terminology will need further definition and clarification. Further investigation is also needed to assess the gluten threshold among individuals with various gluten toxicity profiles.

Haplotypes.

A haplotype is the set of “single nucleotide polymorphism (SNP),” alleles along a region of a chromosome. Some of the segments of the ancestral chromosomes occur as regions of DNA sequences that are shared by multiple individuals. These segments are the haplotypes that enable geneticists to search for genes involved in diseases and other medically important traits (http://www.hapmap.org/originhaplotype.html.en; http://www.genome.gov/10001665).

Heiner syndrome (HS).

A food immune-mediated pulmonary disease that affects primarily infants and is mostly caused by cow’s milk.

Histamine and histamine intolerance.

Histamine intolerance results from disequilibrium of accumulated histamine and the capacity for histamine degradation. Histamine is a biogenic amine that occurs to various degrees in many foods. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the main enzyme for the metabolism of ingested histamine.

HLAs (human leukocyte antigens).

Proteins found on the surface of nearly every cell in the human body. HLAs are found in large amounts on the surface of white blood cells. They help the immune system tell the difference between “self” body tissues and foreign substances.

HLA system.

Major histocompatibility complex (MHC) in humans, controlled by genes located on chromosome 6. It encodes cell surface molecules specialized to present antigenic peptides to the T-cell receptor (TCR) on T cells.

Hypotension.

Blood pressure that is below the normal expected for an individual in a given environment. Hypotension is the opposite of hypertension (abnormally high blood pressure). It is a relative term because the blood pressure normally varies greatly with activity, age, medications, and underlying medical conditions. Unlike high blood pressure, low blood pressure is defined primarily by signs and symptoms of low blood flow and not by a specific blood pressure number. A sudden fall in blood pressure can also be dangerous. A change of just 20 mmHg, a drop from 130 systolic to 110 systolic, for example, can cause dizziness and fainting when the brain fails to receive an adequate supply of blood. Big blood pressure plunges, especially those caused by uncontrolled bleeding, severe infections, or allergic reactions, can be life threatening.

Hypotension for children.

Defined as systolic blood pressure <70 mmHg from 1 month to 1 year, [<70 mmHg + (2 age)] from 1 to 10 years, and <90 mmHg from 11 to 17 years.

Hypoxia.

An abnormal condition resulting from a decrease in the oxygen supplied to or utilized by body tissue.

Immune response.

The action taken by the body’s immune system to defend itself from pathogens. The immune system must be able to determine what is a normal part of the body or “self,” from what is foreign or “non-self.” The immune response can be roughly divided into two broad categories: innate (natural) immunity and adaptive (acquired) immunity.

Immunoglobulins (Ig).

Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies. All immunoglobulins have a four-chain structure as their basic unit. They are composed of two identical light chains (23 kD) and two identical heavy chains (50–70 kD).

Incontinence.

Inability to restrain a natural discharge or feces from the body.

Infantile colic.

Refers to colicky babies who cry constantly and hard at about the same time each day at least 3 days a week. It is more common in boys and in firstborn children. It usually begins at about 2 weeks of age and goes away by the fourth month. Infants who are experiencing symptoms of cow’s milk allergy have a high rate (44%) of colic. However, the role of allergy as opposed to other causes among those with colic and without other symptoms of food allergy remains controversial and in need of additional study.

Innate immunity.

This is a nonspecific, fast-acting response and is not directed against one type of pathogen/antigen, but is capable of destroying many different invaders.

Lymphocytes.

These are types of white blood cell responsible for acquired immunity and may be T cells or B cells. T cells are produced in the thymus, where they learn to distinguish self from non-self. Only the T cells that ignore self-antigen molecules are allowed to mature and leave the thymus. B cells are formed in the bone marrow. They have particular receptor sites on their surface where antigens can attach.

Oral allergy syndrome (OAS).

Oral allergy syndrome is an allergic (immunologic) reaction to certain proteins in a variety of fruits, vegetables, and nuts, which develops in some people with pollen allergies, particularly birch pollen allergies, but it can also affect people with allergies to the pollens of grass, ragweed (more common in North America), and mugwort (more common in Europe). These reactions can occur at any time of the year but are often worse during the pollen season. Oral and/or pharyngeal pruritus appears within minutes after the intake of the food and may be the first symptom of generalized anaphylactic reactions or the only manifestation (http://www.inspection.gc.ca/english/fssa/concen/tipcon/orale.shtml).

Rhinitis.

Allergic symptoms involving the nose (e.g., itching, sneezing) with increased secretion and blockage.

Rhinoconjunctivitis.

Allergic conjunctivitis is also called “rhinoconjunctivitis.” It is the most common allergic eye disorder. The condition is usually seasonal and is associated with hay fever. The main cause is pollens, although indoor allergens such as dust mites, molds, and dander from household pets such as cats and dogs may affect the eyes year-round. Typical complaints include itching, redness, tearing, burning, watery discharge, and eyelid swelling. To a large degree, the acute (initial) symptoms appear related to histamine release.

Sensitivity and specificity.

These terms are used as measures of how good a medical test, sign, or symptom is. The sensitivity of a test refers to how many cases of a disease a particular test can find. On the other hand, specificity of a test refers to how accurately it diagnoses a particular disease without giving false-positive results. See also Gluten sensitivity.

Shock.

Medically, shock is a critical condition brought on by a sudden drop in blood flow through the body. There is failure of the circulatory system to maintain adequate blood flow, curtailing the delivery of oxygen and nutrients to vital organs. The signs and symptoms of shock include low blood pressure (hypotension), over breathing (hyperventilation), a weak rapid pulse (tachycardia), cold clammy grayish-bluish (cyanotic) skin, decreased urine flow (oliguria), and mental changes (a sense of great anxiety and confusion).

Stridor.

A harsh, high-pitched whistling sound, produced in breathing by an obstruction in the bronchi, trachea, or larynx.

Syncope.

The temporary loss of consciousness followed by the return to full wakefulness; fainting.

Systemic reactions.

Several systems within the body are affected simultaneously, including the upper and lower respiratory tracts, cardiovascular system, and gastrointestinal tract. In the context of allergy, this refers to anaphylaxis.

Threshold.

Allergen threshold refers to the levels (exposure amounts) below which it is unlikely that a food-allergic individual would experience an adverse effect. It also applies to the establishment of a limit by statute, below which no regulatory action will be taken.

Toxic peptide.

The term “toxic peptide” has been used to describe any gluten sequence able to induce damage of the intestinal mucosa in celiac individuals. However, this term is now more specifically used to refer to those gluten peptides affecting in vitro cells and intestinal preparations, producing damage in vivo, eliciting the innate response. Whereas the peptide fragments eliciting the mucosal adaptive immune response are termed as “immunostimulatory,” “immunogenic,” or “immunodominant.”

Urticaria.

A common allergic skin condition, transient in nature, characterized by erythematous (red) edematous plaques or wheals within the superficial dermis, usually pruritic (itching), burning, or stinging. The lesions typically result from an inflammatory reaction that induces localized transudation of fluid from dilated small blood vessels and capillaries in the superficial dermis. It can be acute (6 weeks’ duration or less), whereas urticaria recurring frequently for longer than 6 weeks is referred to as chronic.

REFERENCES

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Chapman, J., Bernstain, J., Lee, R., Oppenheimer, J. (2006). Food allergy: a practice parameter. Annals of Allergy, Asthma & Immunology, 96, S1–S68.

Eichenfield, L.F. (2004). Consensus guidelines in diagnosis and treatment of atopic dermatitis. Allergy, 59, 86–92.

FDA Threshold Working Group. (2008). Approaches to establish thresholds for major food allergens and for gluten in food. Journal of Food Protection, 71, 1043–1088.

Furuta, G.T., Liacouras, C.A., Collins, M.H., Gupta, S.K., Justinich, C., Putnam, P.E., Bonis, P., Hassall, E., Straumann, A., Rothenberg, M.E. (2007). Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology, 133, 1342–1363.

Hadjivassiliou, M., Sanders, D.S., Grünewald, R.A., Woodroofe, N., Boscolo, S., Aeschlimann, D. (2010). Gluten sensitivity: from gut to brain. The Lancet Neurology, 9(3), 318–330. Review.

Jesenak, M., Rennerova, Z., Babusikova, E., Havlicekova, Z., Jakusova, L., Villa, M.P., Ronchetti, R., Banovcin, P. (2008). Food allergens and respiratory symptoms. Journal of Physiology and Pharmacology, 59, 311–320.

Johansson, S.G., Bieber, T., Dahl, R., Friedmann, P.S., Lanier, B.Q., Lockey, R.F., Motala, C., Ortega Martell, J.A., Platts-Mills, T.A., Ring, J., Thien, F., Van Cauwenberge, P., Williams, H.C. (2004). Revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization. The Journal of Allergy and Clinical Immunology, 113, 832–836.

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Part I: FOOD ALLERGY AND THE CONSUMER

1

IMMUNE-MEDIATED ADVERSE REACTIONS TO DIETARY PROTEINS

Olga M. Pulido

1.1. INTRODUCTION

An adverse reaction to food is a general term applied to the clinically abnormal response to an ingested food, food ingredient, or food additive. Adverse reactions to food may or may not be mediated by the immune system [1–6]. Nonimmune-mediated adverse reactions to food mimicking food allergy are termed food intolerances and can be the result of toxicity, for example, histamine in scromboid fish poisoning or nonallergic food hypersensitivity (Fig. 1.1) [4–7]. In turn, nonallergic food hypersensitivity (Fig. 1.1) can result from (1) chemical/pharmacological action of food ingredients (e.g., caffeine in coffee, tyramine in aged cheese, sulfites in wine, phenylethylamine in chocolate, or the flavor enhancer monosodium glutamate [8–10]; (2) physiological factors associated with specific characteristics of the host (e.g., lactase deficiency leading to lactose intolerance and deficiency of glucose-6-phosphate dehydrogenase in favism) [5, 11–13]; or (3) others such as psychogenic causes (e.g., eating disorders may present clinical symptoms suggestive of an adverse reaction to food) [6, 14]. Conversely, an adverse reaction to food (Table 1.1) may be mediated by an immunologic response and should be distinguished from food intolerances that do not have an immune basis, but may be similar in clinical presentation [2, 7, 15–17].

TABLE 1.1 Food Allergies: Immune-Mediated Mechanisms, Associated Clinical Presentations, and Most Often Offending Foods

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