Edward J. Hall, MA, VetMB, PhD, DECVIM-CA, MRCVS
Department of Clinical Veterinary Science, University of Bristol, Langford House, Langford
The frequent misuse of the expression 'food allergy' to describe any adverse reaction to food has confused the true meaning of the term 'dietary sensitivity' and our impression of how common it may actually be. A dietary sensitivity is any adverse reaction to food and, as well as food allergy, encompasses food poisoning, food aversion and non-immunological food intolerances, including dietary indiscretion. Such adverse reactions to food (i.e., dietary sensitivities) are undoubtedly common; for example, dietary indiscretion as a cause of clinical signs in dogs is seen in most practices on most days.
Food poisoning is a unique, non-repeatable event, whilst food aversion is poorly defined, and neither will be discussed in detail. Food allergy and intolerance are repeatable, and of these intolerance is probably the more important reaction numerically. However, food intolerance is often confused with food allergy, as both are dietary sensitivities.
Strictly, food poisoning represents the direct action of a toxin released within food by organisms contaminating the food. Botulism is a classical example of food poisoning. However, the definition of food poisoning is often broadened to include infection of the patient by organisms that have contaminated and multiplied in food before being eaten, e.g., Campylobacter and Salmonella. These infections are generally avoidable with hygienic food preparation and correct cooking.
Preferences of dogs and cats for certain foods or food types (e.g., meat versus cereal, canned versus dry food) may be variations of normal behaviour, whereas true food aversion is a psychological problem. In humans, food aversion can take the form of psychological avoidance, where there is an avoidance of food for psychological reasons, or psychological intolerance, where an adverse reaction is caused by emotions associated with the food, which does not occur when the food is given in an unrecognisable form. Whether either truly occur in animals is unclear, but behavioural difficulties associated with hand-feeding are certainly recognized.
Intolerances may be predictable or unpredictable. Accidental ingestion of unsafe foods or inadequately-prepared foods, or substances mistaken as food cause predictable responses in all individuals.
Excessive ingestion of food also has a generally predictable outcome: gastrointestinal (GI) upset if an acute episode, obesity if a chronic problem. Scavenging is a natural activity for many dogs, but can be a significant problem in certain breeds renowned for gluttony. Underlying diseases (e.g., hyperadrenocorticism, malabsorption) may also increase appetite and promote scavenging, pica and even coprophagia. Although again it has a predictable outcome in dogs, dietary indiscretion is a non-repeatable event because no two episodes are likely to be exactly the same. It is therefore usually not possible to elucidate exactly what caused the problem after the event: it may simply be 'dietary overload', but in some cases could even represent true food poisoning.
Unpredictable food intolerances are non-immunological reactions occurring in susceptible individuals as idiosyncratic reactions. The reason for such individual susceptibilities may include differences in the intestinal flora, enzyme activity and permeability, post-absorption metabolism and mast cell stability, any of which may have an underlying genetic predisposition. Milk intolerance in animals is perceived as a common problem but absolute, congenital lactase deficiency is not reported in dogs or cats. However, relative lactase deficiency can be an age-related phenomenon in cats or induced by underlying intestinal disease.
Reactions causing intolerances may have a number of underlying mechanisms:
Pharmacological: ingestion of active compounds that may be directly toxic, or act as enteric hormone stimulators or alter PG & FA metabolism
Mechanical: lack of fibre, or irritants such as bones or 'indestructible' nylon bones
Metabolic: inborn error of metabolism, or unabsorbed or indigestible solute, or enzyme/carrier deficiency
Pseudoallergic (histamine-mediated but non-immunological): high histamine content in food or non-IgE mediated mast cell degranulation
Food allergy is a reproducible adverse reaction to a specific food or food additive with a proven immunological basis1,2. In dogs and cats it is a well-recognized cause of pruritic skin disease, although flea allergic dermatitis and atopy remain more common causes. However, evidence for food allergy causing GI disease is less compelling. This reflects the fact that changing the diet alters not only its antigenic components, but also many other constituents that may have a significant effect on GI function, and without objective evidence that an exclusion diet has abrogated an immune-mediated reaction, true food allergic GI disease cannot be diagnosed.
Genetic predisposition to the development of food allergies may reflect inherent defects in the mucosal barrier and/or the gut-associated lymphoid tissue. Yet environmental factors, such as viral infections may be necessary to sensitize an animal by temporarily disrupting the mucosal barrier and/or immune system, and allow an allergic reaction to be triggered at the next exposure.
Food allergies have traditionally been considered to be IgE-mediated type 1 immediate hypersensitivity reactions, and remote, pruritic, skin disease fits such a model. However acute vomiting and diarrhoea and even urticaria and anaphylaxis immediately following ingestion of specific foods are rarely reported. In chronic GI disease, more complex delayed reactions seem more likely.
The signs in food allergic skin disease are secondary to the primary problem of pruritus. Food allergic GI signs have not been as well characterized and are equally likely to be non-specific:
Weight loss and/or stunting
Most of the veterinary literature suggests that GI and dermatological signs caused by food allergy rarely co-exist, although that view has been challenged3.
The literature suggests that in dogs the most frequent foods incriminated are beef, dairy products and gluten (wheat), whilst in cats, beef, dairy products and fish are apparently significant causes. The prevalence of allergy to different food substances may also be subject to geographic variation, reflecting the nature of the foods most commonly fed. Many proposed breed predilections are largely anecdotal, and it is likely that there are geographic variations, reflecting differences in the gene pool.
A number of histological changes in the gut have been proposed as markers of food allergy:
Intraepithelial lymphocyte infiltration
They resemble some of the histological changes seen in idiopathic inflammatory bowel disease (IBD), and so it may be appropriate to perform a diet trial on every suspected case of IBD, before treating with immunosuppressive agents, in case of it is actually a food allergy.
Diagnosis of dietary sensitivity
This is only possible for repeatable dietary sensitivities (i.e., food allergy and some food intolerances). The cornerstone of the diagnosis is the response to an exclusion diet. The exclusion diet comprises a single novel source of protein and carbohydrate as the sole dietary intake throughout the trial period. Remission occurs by exclusion of a specific dietary component and relapse happens when the patient is challenged with that component. Unfortunately, with the increasing diversity of foodstuffs that pets are exposed to as part of their everyday diet, it is becoming increasingly difficult for clinicians to find a suitable diet for trial, and ever more exotic ingredients are being used to formulate a suitable exclusion diet.
Use of a hydrolysed diet may offer an easier choice of exclusion diet, and have the potential benefit of being less antigenic. However, hydrolysis down to very small, totally non-antigenic peptides often imparts a bitter taste to the product, and so currently marketed products contain molecules that are 5,000-12,000 daltons. These peptides are too small to cross-link IgE molecules bound to mast cells, and should therefore prevent type 1 hypersensitivity reactions. However, they could still carry the same antigenic epitopes that are exposed in normal digestion. Critical appraisal of their efficacy is awaited, although they perhaps are an opportunity to improve our diagnostic yield by providing a completely novel diet.
One of the difficulties of an exclusion diet trial in suspected food allergic GI disease is that cessation of GI signs may not necessarily indicate a true allergy. Reliance on cessation of clinical signs is unreliable, and there is a lack of objective criteria by which to judge the response to an exclusion diet. Repeated intestinal biopsy is the 'gold standard', but the difficulties of obtaining three sequential biopsies (initial, remission, challenge) are considerable. Assessing responses directly by gastroscopic food sensitivity testing is technically demanding, prone to artefact and likely only to detect type 1 hypersensitivities4. Recently colonoscopic allergen provocation (COLAP) has been proposed as an easier technique, but false positives were apparently still common5.
Thus indirect tests for food allergy have been sought. Intradermal skin testing has been unhelpful, but attempts at serological testing for food-specific antibodies have become popular. The presence of food-specific IgG is unlikely to be predictive as such antibody can be found in normal individuals. Food-specific IgE antibody assays should be more specific, but only for the diagnosis of type 1 reactions.
If the patient has a food intolerance rather than a food allergy, there may be no need to avoid immunologically related foods, but inability to distinguish intolerance from allergy usually prevents such a fine distinction. Home-cooked diets are often preferred for the diet trial as the ingredients can be strictly controlled, but they are usually nutritionally unbalanced and not suitable for long-term feeding. Furthermore, in the author's experience, the theoretical advantage of home-cooked diets even for the diet trial is outweighed by the improved owner compliance when feeding commercial foods. Hydrolysed diets may be suitable, but there are a number of gluten-free proprietary exclusion diets based on lamb, chicken or fish available with rice, potato, maize (corn) or tapioca as their carbohydrate sources.
1. Hall EJ. Gastrointestinal aspects of food allergy: a review. J Sm Anim Pract 1994;35:408.
2. Hall EJ. Gastrointestinal adverse food reactions. Prakt Tierarzt 2002;83:30.
3. Paterson S. Food hypersensitivity in 20 dogs with skin and gastrointestinal signs. J Sm Anim Pract 1995;36:529.
4. Vaden, S. L., Hammerburg, B., Davenport D. J., Orton, S. M., et al. J Vet Intern Med 2000;14:60.
5. Allenspach K., et al. Application of a new tool for the diagnosis of food allergy in 10 Dogs: colonoscopic allergen provocation. Proc. 20th ACVIM Forum, Charlottesville 2003.