Author: Philippe Michon
CES Dietetics
Veterinary Clinic
31 rue des ramoneurs
59600 MAUBEUGE
Introduction
The term food intolerances covers all pathologies related to the ingestion of a food, whether immune-related or not.
Knowledge in veterinary allergology is relatively recent and not always perfectly understood.
As early as 3000 BC, a Chinese emperor forbade fish, shrimp, chicken, and horse to pregnant women. The principle of desensitisation has been known since 1941, but the demonstration of the role of immunoglobulin E only dates back to 1973. In dogs, the first observations date back to 1922 (Philips cited by Fourrier(8)). Awareness of their frequency only emerged in 1967 (Walton cited by Fourrier(8)).
Mechanisms of protection against food allergies
Three natural defence systems against the development of food allergies
(according to Hannah 1998)
1 – Protein Digestion
The main allergens being proteins, protein digestion is the simplest and most effective way to combat food allergy. However, some proteins are not sufficiently reduced to be anallergenic.
2 – Gastrointestinal Mucus
Mucus secreted by gastrointestinal cells forms a physical barrier against the absorption of large protein entities.
This barrier can be interrupted during gastroenteritis or colitis.
3 – Peyer’s Patches
The presentation of small amounts of intact dietary proteins to the intestinal lymphoid tissue limits the immune response by activating T-suppressor lymphocytes: this is oral tolerance.
Deficiencies in these mechanisms have a genetic origin. They are evolutionary with age (Ng 2002).
The development of the T lymphocyte immune balance in children is slower in atopics. A hygiene hypothesis is that modern life is associated with too little early bacterial stimulation. This lack of stimulation of the immune system would lead to a deficiency of suppressor T lymphocytes to allergens encountered early in life.
The development of a particular bacterial flora with industrial foods could play a role in the higher proportion of allergies in industrialised countries.
Clinical trials confirm the important role of intestinal flora in allergenic regulation and reinforce the interest of studies on probiotics. (Björkstén 2002)
Malfunctioning of any of these three systems can lead to a food allergy.
4 – Intestinal Epithelial Lymphocytes
Lymphocytes are located in the intestinal lamina propria:
þu CD8 T lymphocytes
þu Natural Killer lymphocytes
þu B lymphocytes producing immunoglobulin A
With Peyer’s patches, they form the SIAM (Système Immunitaire Associé aux Muqueuses) for French speakers, GALT (Gut Associated Lymphoid Tissue) for English speakers.
Mechanism of Food Allergy
True food allergy is a hypersensitivity phenomenon in a genetically predisposed individual. It is an altered immune phenomenon. This immunity remains essential for the individual to fight internal aggressions (tumors) or external ones (viruses / bacteria). It always begins with a sensitisation phase without clinical expression, of variable duration.
* Guaguere and Prélaud (11) however report a racial predisposition in Shar-Pei and Ig A deficiencies also in Cockers, German Shepherds, and Beagles. The German Shepherd deficit would be reversible after 1 year of age in 80% of cases.
In the United States, food anaphylactic shocks are fatal in 0.5% of cases in humans and mainly concern peanuts, nuts, fish and shellfish. (Sampson 2000)
Concept of Threshold and Summation
Pruritus is only triggered when an allergenic stimulation threshold is reached.
– The different antigenic stimulations add up (summate) and this addition can lead to exceeding the threshold.
The theory distinguishes these cases from food intolerance, in which the symptoms encountered during food intolerance are urticaria, angioedema (Quincke’s edema) and sometimes diarrhoea.
They are due to pro-inflammatory substances directly released by food: bioamines, histamine and tryptamine. The most commonly involved foods are canned or frozen meats and fish, seafood, egg white, chocolate and cheese (Fourrier 1991). Tuna poisoning linked to histamine not destroyed by cooking has recently been described in humans (Ohnuma 2001). Such bioamines can also be found during intestinal bacterial proliferation.
Lactose intolerance linked to a decrease in lactase activity in some adult dogs causes essentially intestinal symptoms. Similarly, gluten enteropathy in Irish Setters only causes intestinal symptoms. These entities are also included in food intolerances.
IMPORTANCE
According to certain published results, food allergies would be involved in 62% of non-seasonal pruritus cases (Leib 1989). A Canadian study (Cited by 11) reveals an improvement in symptoms in 20% of non-parasitic pruritic allergies after using a diet. They can be associated with other allergies, thus contributing to the threshold effect and the summation of effects. Thus, 63% of humans with food allergy are also atopic and 35% of atopic children concurrently have a food allergy (Hillier 2001); up to 30% of atopic dogs would also be food allergic and vice versa (Hillier 2001). Hormonal hypersensitivity associated with food allergy has even been reported (Prost 1995). Lowering the allergenic stimulation threshold by eliminating food allergy can prevent or reduce the treatment of other allergies.
While 2/3 of cases concern animals older than 1 year, food allergies can be encountered as early as 6 months and exceptionally earlier. However, Fourrier recommends prioritising food allergy in any non-parasitic pruritus in a puppy under 6 months. Hoskins in 1990 considers food allergy to be common in young dogs in association with recurrent pyoderma.
No sex predisposition has been noted; however, certain breeds appear to be predisposed (White 2001): Dalmatian, West Highland White Terrier, Collie, Shar-Pei, Lhasa Apso, Cocker, Springer, Miniature Schnauzer, Retriever, Boxer.
Most frequent allergens
The most common allergens are glycoproteins with a molecular weight of 18,000 to 36,000 δ. Any food protein is potentially allergenic because it is recognised as a foreign protein by the animal’s immune system.
The first three represent more than 50% of cases in a sample of 25 dogs (Harvey 1994).
According to 11:
þu In Great Britain: Beef + soy + milk + cereals + chicken + corn + wheat + egg.
þu In Canada: Beef + dairy products + eggs + chicken.
þu In France: Beef + milk + Rice + fish + egg.
A food colouring derived from a fungus Monascus purpureus, has recently been identified as a cause of allergy in German sausages (Hipler 2002). However, for Guaguère and Prélaud (11), reactions to food additives are rare in humans and have never been proven in dogs and cats. The implicated additives are colourings, flavour enhancers and preservatives. Given their small size, they must bind to proteins to express an antigenic power: haptenization phenomenon.
Structure and Allergenicity
According to Aalberse Stapel 2001
The three-dimensional structure of many allergens is now known.
Most of these structures can be grouped into 4 categories:
1°) α-helical proteins: napins (proteins with double sulfur bonds contained in glumes) and α-lipid transport proteins; lactalbumin: a close structural relationship exists between bovine α-lactalbumin and hen egg white lysozyme.
2°) β-helical proteins: (lipocalin such as profilins β-lactalbumin).
Plasma proteins transporting retinol in humans and cattle are 92% homologous.
3°) α β proteins: Lactabumine
4°) Serpines (SERine PRotease INhibitor): such as ovalbumin, which despite its structural similarity is not a protease inhibitor.
In addition to these 3-dimensional structures, the structure of the lateral carbohydrate chain is responsible for cross-allergies between plant-derived foods and invertebrates.
The lateral carbohydrate chains and profilins are not complete food allergens: they only induce food allergy through cross-reaction, often with pollen allergens.
Serum albumins are the most common source of cross-allergy between mammals. Such a cross-reaction has never been demonstrated between mammalian and avian albumins.
Can the similarity of exogenous proteins with endogenous proteins increase their allergenic potential?
Many questions remain unanswered.
Diagnosis
Given the phenomena of threshold, summation, and the frequency of associations with other allergies, any recurrent pruritus should suggest food allergy. The response to corticosteroids cannot, for these same reasons, rule out the presence of an allergy. Sometimes an external otitis may be the only symptom. A study found that 10% of ear infections are due to food allergies (Carlotti 1997); if parasitic causes are eliminated, the percentage rises to 17.4%.
Unlike humans, allergy symptoms are almost exclusively cutaneous in dogs. An association with pyoderma and/or malassezia is common. Pyoderma can even be the only symptom with an absence of pruritus.
Associated digestive signs are uncommon, less than 15% of cases, and may go unnoticed. Rare cases of associated epilepsy have also been described (Rosser 1999).
ANY PRURITUS SHOULD SUGGEST FOOD ALLERGY
Laboratory tests are of little use
- Eosinophilia is rare,
- Histopathology is not specific,
- Intradermal tests are unreliable, unlike their excellent negative predictive value in humans (Corbin 1995)
- Only Ig G assays and basophil degranulation tests may have some reliability. However, it should be noted that errors by default are numerous for Ig G assays. Furthermore, basophil degranulation tests give very irregular results (Muller Héripret 1997)
- White in 2001 confirms great disappointment with both skin and serological tests.
Current knowledge leads to considering true food allergies as allergies to a protein structure rather than to a food.
The treatment of food allergies must take into account this new data and avoid cross-reactions, for example, between different mammal albumins. These reactions may be the cause of the failures of diets where only beef is replaced by lamb or horse in cases of beef allergy, for example.
