Cutaneous Food Allergy in Animals
(Adverse Food Reactions)
Food-induced diseases may be categorized into:
true hypersensitivities (IgE-mediated or otherwise)
metabolic syndromes (eg, lactose intolerance in people and small animals)
pharmacologic reactions (eg, GI and neurologic disturbances after ingestion of methylxanthines in chocolate or hypoglycemia after ingestion of xylitol)
toxic reactions (eg, mycotoxins, renal failure from exposure to melamine in pet foods)
Together, these conditions are broadly characterized as "adverse food reactions." This discussion focuses on cutaneous food-induced hypersensitivity reactions ("food allergies").
Food allergies have been best characterized in small animals. Although it is likely that large herbivores also suffer from food-induced hypersensitivity reactions, identification of food allergy in large animals is complicated by the difficulties associated with completely controlling food intake in animals not housed in confinement. Only anecdotal reports about horses with food allergies are available in book chapters but not in peer reviewed publication.
The true prevalence of food allergies in dogs and cats is unknown. A recent literature review of 28 high-quality manuscripts found that the reported prevalence of food allergy varied depending upon the specific population evaluated. For example, 1%–2% of dogs and <1% of cats presenting for any form of veterinary care were found to have some form of food allergy. This percentage increased considerably in pets presenting for any form of dermatitis (0%–24% of dogs; 3%–6% of cats) or pruritus (9%–40% of dogs and 12%–21% of cats).
The most common food allergens often correspond with the most commonly fed food sources. A recent review reported the most common food allergens in dogs and cats (see Table: Types of Food Allergens in Dogs and Cats). Animals may demonstrate hypersensitivity to more than one food source.
In contrast to environmental allergen-associated atopic dermatitis (in which the majority of patients initially demonstrate signs at 1–3 years of age), the age of onset of food allergy is highly variable. Although both cats and dogs with food allergy typically also develop clinical signs in young adulthood (1–4 years old), the age of onset in dogs has been reported to range from <6 months to 13 years, and in cats from 4 months to 15 years. Thus, food allergy may be a particularly likely differential in patients initially presenting with skin disease at either a very young or very advanced age.
There does not appear to be a clear sex predisposition in either cats or dogs. Breed predispositions vary somewhat depending upon local breed prevalence. However, in most western countries, German Shepherds, Labrador Retrievers, French bulldogs, and West Highland White Terriers appear to be over-represented. There is no clear breed predisposition in cats.
The clinical signs associated with food allergy are highly variable. The most commonly reported cutaneous clinical sign in dogs is pruritus. The distribution of pruritus may be generalized or focal/multifocal. Areas typically affected include the pinnae, feet, ventrum, and (less commonly) the perianal/perigenital skin. The pruritis associated with food allergy can be as severe as that caused by scabies in dogs.
Other common signs of food allergies in dogs include otitis externa (with or without secondary infection) and relapsing infections with Staphylococcus spp or Malassezia. Secondary infections can even occur in patients with food allergy that are pruritus free when infections are controlled. Less common cutaneous manifestations include urticaria, angioedema, or pyotraumatic dermatitis.
As in dogs, the most common clinical sign associated with food allergy in cats is pruritus, especially intense pruritus of the face and head. Pruritus of the ears, ventrum, feet, or more generalized self-inflicted alopecia may also be seen. Other signs include lesions of the eosinophilic granuloma complex and miliary dermatitis.
Both dogs and cats may simultaneously demonstrate both cutaneous and noncutaneous signs of food allergy. GI disease is the most frequently reported comorbidity. Although GI signs may include obvious abnormalities such as vomiting and diarrhea, more subtle manifestations may include increased frequency of defecation (>3 times per day), soft-formed stool, tenesmus, flatulence, and borborygmi. Patients may demonstrate varying degrees of weight loss.
Less commonly reported comorbidities include anaphylaxis, asthma or respiratory distress, conjunctivitis, hypersalivation, hyperactivity, and nasal discharge.
Regardless of the appearance, clinical signs are typically nonseasonal. However, waxing and waning disease may be seen in patients not consistently receiving the same diet(s). Nonseasonal signs with seasonal exacerbations may be seen in patients exhibiting both food allergy and environmental allergen-induced atopic dermatitis.
To date, the only reliable method for the diagnosis of food allergies is a dietary elimination trial. Numerous other diagnostic methods have been investigated (and in some cases, marketed), including ELISA-based serology to detect anti-food IgE, intradermal testing, and hair or saliva analysis. However, none of these methods have given consistently accurate results (ie, correlation with clinical reactivity).
More recently devised diagnostic tests include western blot-based serologic analysis and patch testing. A recent study evaluating the efficacy of a commercially available western blot serologic assay for canine IgE against certain foods found that the assay may help identify some foods to which the patient is intolerant (and thus should be avoided in elimination diet trials), but that negative results did not necessarily correlate with clinical tolerance.
Patch testing with raw and cooked food extracts has also been demonstrated to aid in the selection of foods for a potential elimination diet. In this case, negative results to the food typically correspond to foods to which the patient is tolerant (and thus can be selected for use in elimination diet trials), but positive results were not necessarily associated with clinical intolerance.
The authors of both the western blot and patch testing papers concluded that the techniques may aid in the selection of an elimination diet, but that neither technique was sufficient to diagnose food allergy on its own.
Food allergy elimination diet trials are typically conducted using novel protein diets (whether commercially available or home-cooked), hydrolyzed diets, or diets containing both novel and hydrolyzed proteins. Novel protein diets must be carefully selected to avoid previously fed ingredients. The selection of an appropriate novel protein may be complicated by the potential for allergenic cross-reactivity. Thus, it may be prudent to avoid selecting diets that contain species similar to those previously fed (eg, lamb in patients previously fed beef or milk). In addition, there is some experimental evidence suggesting cross-reactivity between chicken, whitefish, and salmon, although the clinical relevance of these findings is unclear as of yet.
Hydrolyzed diets are those in which the constituent proteins have been broken into smaller fragments, which are more difficult for the immune system to detect and react against. These diets may be categorized as partially hydrolyzed (generally below 5 kilodaltons) or extensively hydrolyzed (generally below 3 kilodaltons, although some extensively hydrolyzed diets are broken into fragments of 1 kilodalton or smaller). Partially hydrolyzed diets may be sufficiently broken down as to be tolerable to an animal sensitized to their source protein, but some sensitized animals may still react to these diets. Extensively hydrolyzed diets are less likely to cause clinical responses, even in animals sensitized to their source protein. These diets may be better suited than partially hydrolyzed diets for the diagnosis of food allergy. However, once the diagnosis has been made, patients may be evaluated to determine whether they will tolerate a partially hydrolyzed diet.
Regardless of the diet format chosen, the pet should be fed that diet exclusively for the period of the elimination diet. The recommended duration of elimination diets varies between practitioners, but a recent literature review found that a minimum length of 10 weeks may be required to identify 95% of food-allergic patients.
Although the selection of an appropriate elimination diet is critical for the diagnosis of food allergy, the elimination of other sources of food proteins is equally important. Clients should be made aware that any food-based item cannot be fed, including rawhide chews, pill pockets, table food, flavored vitamin and mineral supplements, some oral arthritis supplements, and flavored toys. Patients should either be fed separately from other animals in the house or all animals should be fed the same diet. There is also potential for cross-contamination if pets share a water bowl. Patients with a tendency to eat the feces of other animals should be prevented from doing so. Chewable or flavored heartworm preventives or flea medications generally contain beef, pork, or soy protein, regardless of whether this ingredient is listed on the label; unflavored, injectable, or topical products should be used instead. Medication capsules may be made of beef or pork gelatin. If medication in capsule form must be given, it may be best to have the client open the capsule and empty the contents onto the patient's food.
Secondary infections (with Staphylococcus spp or Malassezia) are common in food-allergic patients, and the discomfort associated with these conditions may complicate an accurate assessment of the patient's "baseline" level of pruritus, ie, that associated with the allergy alone. Alternately, a client may find it overwhelming to administer multiple medications and topical products simultaneous with instituting a very restricted diet. In these cases, it may be appropriate to treat the patient's secondary infections before beginning the elimination diet.
The pruritus and discomfort associated with food allergies can be severe, leading to significant self-trauma. This trauma may itself contribute to an inflammatory response and help to perpetuate pruritus. For this reason, patients may receive any antipruritic medication necessary to control their signs during the diet trial. However, the medication must be stopped at least a week or two (longer, in the case of repositol steroid injections) before the end of the trial so an accurate assessment of any residual pruritus can be made.
Clients may find it helpful to keep a diary of their pet's responses during the elimination diet. This diary could be as simple as the date and degree of pruritus (or other clinical signs). Unusual events (visitors, trips to dog parks, etc) should also be included, because they may help to identify potential breaks in the diet. These diaries are particularly useful to provide relatively objective evidence of improvement in animals that are only partially diet-responsive.
At the end of the elimination diet, the patient should undergo a controlled dietary rechallenge. The purpose of the rechallenge is two-fold: to identify problematic food items and to confirm that any improvement is truly associated with the diet and is not coincidental (seasonal allergen changes, better flea control). This may be particularly important if the response to the diet is only partial. In this case, a positive rechallenge demonstrates the presence of food allergy, but the lack of complete remission suggests that a second problem (environmental allergen-associated atopic dermatitis, flea allergy, etc) is likely also present.
Ideally, the rechallenge is conducted using specific ingredients (chicken, beef, etc), but this is not always practical. In that case, a challenge with previously fed food sources (kibble, heartworm preventive, etc) may be performed instead. An increase in itching or other clinical signs is typically evident within days (sometimes hours) of the challenge, but positive challenge responses can take as long as 10–14 days to appear. For this reason, individual food items should not be introduced any more frequently than every 2 weeks so there is no confusion regarding the offending item.
If patients demonstrate a positive response to the challenge, they should be placed back on the elimination diet. Once the patient is comfortable again, the challenge process can resume with other individual proteins so that any other food allergen sources can be identified. Once the diagnosis of food allergy is made, the client may elect to continue the patient on the test diet (if the diet is balanced for longterm feeding) or they may cautiously experiment with other diets to find foods the pet may tolerate.
Recent work has suggested a loose association between the longterm feeding of some diets with an elevated risk of the development of dietary-induced dilated cardiomyopathy in dogs. Suspect diets have included "boutique diets" made by small manufacturers, diets containing exotic ingredients, and grain-free diets. Other potentially problematic diets include those with high levels of legumes (lentils, peas, chickpeas), potatoes, or sweet potatoes. Golden Retrievers appear to be particularly predisposed, but any breed may be affected. It is important to understand that the nature of this association is still unclear—not all diets meeting these descriptions appear to be associated with problems, and dogs can certainly develop cardiomyopathy while eating diets that do not meet this description.
If a patient must be maintained on one of these diets longterm, they should be monitored carefully for signs suggesting possible cardiac disease (coughing, weakness, exercise intolerance, fainting, etc) Periodic measurement of serum taurine levels may be advisable. Echocardiographic evaluation of high-risk breeds (such as Golden Retrievers) may be warranted.
The most common cutaneous clinical sign of food allergy in both dogs and cats is pruritus.
The most common food allergens in dogs are beef, dairy products, chicken, wheat, and lamb, whereas the most common food allergens in cats are beef, fish, and chicken.
A strict dietary elimination trial remains the only reliable method for the diagnosis of food allergies.
Longterm feeding of some diets has been loosely associated with the development of dietary-induced dilated cardiomyopathy.