Adverse Reactions To Food In Dogs And Cats
by: Mark E. Rogers
Many people claim their dog or cat has food allergies. Some present blood test results or skin test results, others just describe the elimination of symptoms after a dietary change as evidence of food allergy. There seems to be a great deal of discussion and confusion on this subject. Most estimates indicate that less then 10% of all dogs and a slightly higher percent of cats have true food allergies. Even these estimates are difficult to verify because, more often then not, more then one condition is present in the animal.
We present here a brief introduction to the subject of allergies and specifically food allergy. We will try to shed some light on the distinctions between true food allergy or food hypersensitivity and merely a food intolerance. Our aim is to provide the best available scientific understanding of this complex issue and perhaps help people make more informed decisions on the proper care and feeding of their animals.
Before we discuss food allergies we feel it prudent to give a brief introduction to what an allergic response is and how the body responds to the introduction of a foreign substance, an allergen.
An allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when an animals immune system reacts to a substance that is normally harmless. A substance (including pathogens or molecules) that elicits an immune response is called an antigen, in the specific case of an allergy it is called an allergen. An allergy is the body’s inappropriate response to a substance that should be harmless but for reasons that are as of yet unclear, the body reacts to them as if they were a foreign invader similar to what it does with pathogenic bacteria and viruses. It is the body’s attempt to remove the allergen from the system. Allergic reactions cause an inflammatory response and these can range in severity from uncomfortable, to dangerous, or even fatal.
An allergic response is primarily to a protein of sufficient size to interact in a unique way with an antibody. Antibodies, the exquisitely adaptable soldiers of the immune system, are designed to recognize and remove foreign invaders. When the invaders are viruses or bacteria the antibody binds to the cell surface of the bacteria or protein coat of a virus and begins a series of biological mechanisms designed to remove the invading body. In an allergic response, the antibody binds to the protein that is perceived to be a foreign invader and this sets into motion a series of inflammatory reactions. Small molecules can also trigger an allergic response. This however, can only occur if the small molecule binds to the surface of a cell in the body or to a protein that is a normal part of the animals system. Small molecules that elicit an immune response are called haptens. Examples of small nonprotein molecules include the Urishiols in Poison Ivy, and sulfa drugs and penicillin type antibiotics.
Antibodies are protein structures that exist in animals as a major component of the immune system and have very specific features. A primary feature is that they have a Y shape. They are comprised of two chains, the heavy chain and light chain, so named because of their size and amino acid content. The two chains are bound to one another through disulfide bonds (sulfur linkages) and each has a variable region and a constant region. Figure 1a. The variable regions are the site of antigen binding. They are unique to each antibody and antigen, or binding site on the antigen.
There are five main isotypes (types) of antibodies also known as immunoglobulins. Each is designated by Ig and another letter following the g to denote the specific isotype. IgA and IgE are the isotypes most important in the allergic response. Although animals start life with only a relatively small number of antibodies - tens of thousands- through very elegant and complex mechanisms a healthy animal will produce tens of millions of unique antibodies over a lifetime! Changes in the variable region allow for this incredible diversity. The beauty of antibodies is illustrated below. Figure 1b.
General Considerations
An adverse reaction to food can be defined as an abnormal response to an ingested food or food additive. They can be classified into two groups. Those that have an immunologic basis are termed food allergy or food hypersensitivity. Those that are have a nonimmunologic basis are best termed food intolerances. These two pathologies are very different though their manifestations and symptoms may be very similar and difficult to distinguish. The fact that food related reactions appear relatively infrequently (given the estimated 78 million dogs and 86 million cats in the US) is testimony to the effectiveness of the gastrointestinal mucosal barrier and oral tolerance. Adverse reactions to foods have been blamed for a variety of clinical syndromes and usually involve the skin and gastrointestinal (GI) tract.
Carefully controlled prevalence studies in cats and dogs have not been done. The major problem with establishing prevalence is that adverse food reactions mimic other diseases especially puritic (itching) dermatosis and often coexist with other allergic conditions. Veterinary dermatologists suggest that adverse reactions to food account for 1-6% of all dermatoses and food allergy constitutes from 10-45% of all allergies in dogs and cats. The other two more common causes of hypersensitive skin disease in cats and dogs is flea allergy and atopic dermatosis caused by environmental allergens, e.g., pollen, mold, dust, etc. Although most adverse reactions to foods that cause dermatosis have been blamed on food allergies, no specific tests have been performed to confirm an immunologic basis for the clinical symptoms.
Adverse reactions to food also appear to be an important source of gastrointestinal distress in dogs and cats. It is unknown if food allergy or food intolerance is the primary cause of the GI abnormalities or if they are exasperated by some undiagnosed underlying disease. Modifying a diet with concomitant alleviation of clinical GI symptoms may just relieve the problem temporarily without treating the underlying cause.
Dermatologic Signs Of Adverse Food Reactions In Dogs
Reports of adverse food reactions in dogs with skin disease have not documented a breed or gender predisposition and ages range from 4 months to 14 years. West Highland white terriers do appear to be at higher risk. Lesion (sore) distribution is indistinguishable from atopic dermatitis resulting from environmental allergens. Common areas are; face, feet, underarms, anal region, groin area, and ears. Adverse food reactions and environmental atopic dermatitis should be considered in dogs that present with nonseasonal dermatopic disease.
Adverse food reactions in dogs do not produce a set of specific signs on the skin and mimic many other non-food allergies and non-allergy associated skin disorders. An estimated 30% of dogs with suspected adverse food reactions may have concurrent allergic diseases such as environmental allergies and/or flea allergy.
Dermatologic Signs Of Adverse Food Reactions In Cats
The age of cats effected by adverse food reactions range from 6 months to 12 years. There is no gender or breed predisposition although Siamese cats and Siamese-cross cats show an increased risk. Dermatologic signs include; severe generalized itching without sores, rash with sores, itching with self inflicted trauma, self induced hair loss, scaling. Similar to dogs, as many 30% or more of cats with adverse food reactions may also suffer from concurrent environmental allergies and/or flea allergy.
Gastrointestinal Responses to Adverse Food Reactions in Dogs and Cats
Every level of the GI tract can be damaged by food allergies. Clinical allergies usually relate to the stomach and small intestine dysfunction but colitis can also occur. Vomiting and diarrhea are also prominent features. The diarrhea may be profuse and watery, mucoid ( filled with or resembling mucus), or hemorrhagic (filled with blood). GI disturbances occur in about half of dogs and cats with skin manifestations of food allergy.
The role of food allergy in canine and feline IBD (irritable bowl disease) is unknown. Hypersensitivity to food is probably involved in the development or progression of this syndrome in some animals. In some of these instances the animal may more appropriately be diagnosed with food protein-induced inflammation of the small and large intestine. Dogs with GI disease show more food allergen specific antibodies then normal dogs. This finding may reflect a greater antigen exposure due to increased permeability of the mucosal membrane in the early GI tract.
Findings from a technique called Gastroscopic Food Sensitivity Testing (GFST) indicate that food allergy is involved in perpetuating IBD but may not be a primary cause. That is, inflammation of the mucosa predisposes an animal to acquired food allergies. Thus, proper early treatment of the underlying cause of the IBD may prevent development of food allergy. This also suggests that a change in diet and thereby food allergens may temporarily alleviate the immunologic aggravation of the inflammatory disease. However, the duration of this effect may be short and is a highly questionable treatment option. It may simply be that the novel but intact proteins of the new diet have not yet elicited an immune response. The underlying mucosal permeability problem has not been eliminated and sooner rather then later clinical signs reemerge. Depending on how porous the membrane has become strongly influences the duration of relief from clinical signs that the new diet can provide. Irritable bowel disease is characterized by recurrent, chronic abdominal pain and diarrhea. Diet changes as described above may temporarily alleviate symptoms but a more effective solution has been to avoid gas forming vegetable based diets and high fat diets. Together these results indicate the presence of food intolerance resulting from the primary IBD and not true food allergy.
Diagnostic Methods and Risk Factors
The ONLY diagnostic method of any value is elimination diets followed by single ingredient challenge and rescue protocols. This is the only way to accurately determine what food ingredients may be true allergens. It is important to note that diet trials confirm or rule out adverse food reactions but do not indicate the underlying mechanism as immunologic or nonimmunologic (food allergy or food intolerance)!
The risk factors for adverse food reactions in animals are currently unknown. They may include; certain foods or food additives, poorly digestible proteins, any disease that increases the intestinal mucosal membrane permeability, e.g., viral infection, selective immunoglobulin (IgA) deficiency, genetic predisposition, concurrent non-food allergic disease.
The Development of Food Hypersensitivity
Mucosal Barrier and GALT - Structure and Function
The ingestion of food represents the greatest load of potentially antigenic material presented to the immune system. The defense against hypersensitivity to food includes an effective mucosal barrier and oral tolerance generated by the cellular immune system of GALT, (GALT = gut-associated lymphoid tissue). (GALT is a convenient acronym used by scientists to describe the entire cellular immune system that substances encounter when they are ingested through the mouth. It includes everything from the tonsils to the rectum.)
An important adaptation of the GI tract is the development of a mucosal barrier that prevents the overwhelming uptake of food antigens. Efficient functioning of the mucosal barrier excludes the majority of ingested antigens, thus minimizing antigen exposure to GALT. The mucosal barrier includes effective digestion, the mucosal layer, intact and functioning epithelial cells and antibodies of the IgA isotype. Figure 2.
Complete digestion of food proteins results in free amino acids and small polypeptides that are poor antigens. Incomplete digestion of proteins results in large polypeptides that have the potential of eliciting an antigenic (immune) response. The mucous layer overlaying the intestinal lining contributes to the defense against antigen attachment and penetration into the interior layers of the intestine. The mucous contains carbohydrates that can bind to antigens and prevent their contact with the microvillous surface, (microvillous = large numbers of small projections on the surface of cells). Additionally, IgA is the major immunologic component of the mucosal barrier because it is present in large concentrations in intestinal secretions. IgA may bind to food antigens preventing their transport to the interior structures of the intestine and GALT. Figure 2.
Despite the defense mechanisms, the mucosal barrier is not completely impervious to food proteins. Some still cross the barrier in small but significant quantities. These proteins are removed by large immune cells called macrophages produced by the liver and lymph nodes associated with the GI tract.
The intestine, normally considered an organ of digestion and absorption of nutrients plays a critical role in the immune system. The GI tract is probably the largest immune organ in the body. GALT is composed of four distinct lymphoid compartments. The exact names are given below along with a schematic representation and brief description of their function. It is provided to show not only the complexity of the system but also the elegant beauty and intricacy of an animals defense against invading pathogens and unwanted antigens. The interested reader is encouraged reader is encouraged to explore this system in greater detail at their leisure.
GALT: 1) aggregates of lymphoid follicles throughout the intestinal mucosa, 2) lymphocytes and plasma cells scattered throughout the lamina propria (bottom membrane), 3) intraepithelial lymphocytes integrated between enterocytes, and 4) mesenteric lymph nodes (mesenteric = a fold that attaches the organs of the gut to the wall of the abdomen). Figure 3.
Although GALT must mount a rapid and potent response against potentially harmful foreign substances and pathogenic organisms, it must also remain unresponsive to enormous quantities of food antigens. Absorbed food antigens are presented top GALT in such a way that a potent immune suppressive response develops. Figure 4.
This immune suppression response, along with an absence of normal immune response to foreign proteins and cell deletion form the basis of oral tolerance. Conversely, an allergic response can develop if the food antigen encounters a defective component of GALT or escapes into the circulatory system. It is important to note that since the GI tract lymphoid immune system responds to food antigens by active mechanisms it is possible that anything that disrupts, overloads, or in anyway prevents near perfect functioning of this system can result in clinical allergic signs rather then immune tolerance.
Potential Mechanisms for Allergy Development
Abnormalities in the gastrointestinal defense mechanisms may predispose animals to food allergies. Predisposing factors for food allergies may include: 1) mucosal barrier failure (poorly digestible proteins, incomplete protein digestion, increased intestine mucosal barrier permeability, age related changes in cell composition and structure, inflammation-induced changes in mucosal structure), and 2) decreased immunoregulation (decreased IgA secretion, dysfunction of cell mediated responses of GALT, monocyte-macrophage dysfunction). Figure 4.
Conclusions
We have examined the subtle but important differences between true food allergy and food intolerance. We have looked at the many difficulties in assessing wether clinical symptoms are the result of food allergy, non-food allergy, non-allergy skin disease, or non-food GI disease. Looking at the complex systems of the GI tract, the mucosal barrier and GALT, we have seen that although these systems function with incredible efficiency and many defensive capabilities, any of one or several of these defenses can break down and cause food intolerance or food allergy. One thing we have not discussed is the foods themselves.
Most companion animals are fed a commercial diet or some combination of diets. The sourcing of ingredients, the quantities of ingredients, combinations of ingredients, and processing methods vary considerably in these foods. Any one of these alone or in combination can influence the antigenicity of the ingredients. The specific food allergens or ingredients that cause problems in dogs and cats have been poorly documented. That is to say, chicken is not necessarily chicken. The various organs and other chicken portions are made up of different proteins. How they are combined with other ingredients especially before cooking and otherwise processed can have a dramatic effect on the structure of the resulting proteins in the food. This in turn will effect their digestibility and how they present to the mucosal barrier and oral tolerance.
The influence of other allergic conditions, and/or diseases can influence a particular ingredient or combination of ingredients as a source of food allergy or food intolerance. The lack of clear cut symptoms, tests, and treatments all complicate the issue of food allergy in cats and dogs. All these and many more make one thing abundantly clear. There is no simple answer or simple solution!
Perhaps the best course of action for us to take as the caretakers of our beloved animals to care for and feed them to the best of our ability can be summed up in this way. Provide for them variety in their diet. Feeding them one food throughout their lives will only increase the likely hood that food proteins will at some point become food antigens. Feed them the highest quality foods we can as we would do for ourselves. Finally look to the best available science, not emotion, marketing, advertising, hype, and here-say for information and direction. We call them our best friends. Together lets treat them as we would surely want them to treat us if the roles were reversed!
References
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Proceedings of the World Small Animal Veterinary Association Sydney, Australia – 2007, DISTINGUISHING BETWEEN ALLERGIES Peter J. Ihrke, VMD, Diplomate ACVD, Department of Medicine & Epidemiology, School of Veterinary Medicine University of California, Davis, California, U.S.A.
PROCEEDINGS OF THE NORTH AMERICAN VETERINARY CONFERENCE VOLUME 20
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FOOD ALLERGY DERMATITIS
Sarah Colombini Osborn, DVM, Diplomate ACVD Southwest Veterinary Dermatology Houston, TX
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