Diagnosis

The “gold standard” for the diagnosis of food allergy in humans is a double-blind placebo-controlled food challenge.³ When food allergy is caused by a Type I (IgE- mediated) immediate hypersensitivity, an in vitro serum testing for food-specific IgE antibodies is of diagnostic value.

In contrast to the case with humans, serological testing or intradermal testing for cutaneous adverse food reaction is of no value in dogs and cats.^4,5 A previous study revealed that serum testing had a 40% positive predictive value (percentage of positive test results that were true positives) and a 60.9% negative predictive value (percentage of negative test results that were true negatives).¹⁵ In a study performed with normal dogs, dogs with cutaneous food reactions, and those with skin diseases other than cuta­neous food reactions, all the healthy dogs and 75% of the dogs with cutaneous food reactions had positive serum tests for food antigens.

Such a finding may indicate that in dogs and cats cutaneous food reaction is not an IgE-mediated disease, or that the antigens tested are not the same as those that are causing the reaction. This may be due to changes in the antigens that occur during manufacturing and digestion. Also, test antigens for animal proteins, whether used for serologic or intradermal testing, are frequently derived from skeletal muscle, while chicken by-product meal is used in commercial dog and cat food. Chicken by­product meal from tissues from the neck, back, and viscera are antigenically different from skeletal muscle.⁹

Therefore, as in humans, the gold standard for diagnosing cutaneous adverse food reaction is an elimination-diet trial followed by a provocative challenge. Currently there are two schools of thought regarding how an elimination-diet trial may be performed. One group believes that a home-prepared diet consisting of a novel protein and novel carbohydrate is the only proper way to diagnosis cutaneous adverse food reactions. There is also a group that believes that a commercially prepared diet is appropriate to diagnosis cutaneous adverse food reactions. There are two types of commercially prepared “hypoallergenic” diets available on the market: novel protein source foods, and hydrolyzed proteins. The author believes that the commercially available diets may rule in adverse food reaction but cannot rule it out.

Novel protein diets contain such unique ingredients as venison, rabbit, duck, salmon, catfish, and kangaroo as protein sources, and either potato, rice, oat, or barley as carbohydrate sources. The basis of these diets is that individuals are allergic only to antigens to which they have been exposed previously. However, in one study of 40 dogs proven to have cutaneous adverse food reaction based on a home-prepared diet, recurrence of pruritus occurred in 52.5% fed a commercial chicken/rice dog food, 47% on a catfish/rice dog food, and 85% on venison/rice dog food, even though these ingredients were thought to be novel to them.¹⁷ In another study, 50% of eight dogs with cutaneous adverse food reaction (also identified with home-prepared diets) were intolerant of a commercial catfish/rice diet.¹⁸ In a double-blinded study of 20 cats with cutaneous adverse food reaction, the authors evaluated two commercial hypoallergenic diets.¹⁹ The cats were diagnosed as having cutaneous adverse food reactions based on resolution of clinical signs when fed a home-prepared diet.

Hydrolyzed protein diets use common protein sources such as soy, chicken liver, or casein, which have been enzymatically hydrolyzed to such short peptide chains that, theoretically, the immune system should not be able to recognize them as the parent proteins. In food-allergic people, most major food allergens are water-soluble glycoproteins with molecular weights ranging from 10,000 to 70,000 daltons and are stable to treatment with heat, acids, and proteases. However, some proteins have been reported not to become antigenic until they are heated or digested.³’⁴ In humans it has been reported that the immune system cannot recognize a molecule smaller than 12,000 daltons.³ Although characterization of the physiochemical properties of most major food allergens in dogs and cats has not yet been performed, hydrolyzed products currently available in veterinary medicine have used a 5000- to 10,000-dalton particle size as their “ideal” cutoff. However, it is possible that the size of the anti­gens that may cause immunologic reactions in dogs may be smaller than in humans.³ It has been reported that in a group of three casein-hypersensitive dogs, the antigen that was responsible for the reaction was between 1100 and 4500 daltons.³ Products currently available use hydrolyzed chicken/chicken liver (Hill’s Prescription Diet Z/D Low Allergen), hydrolyzed soy (Purina CNM LA Formula), and hydrolyzed casein and liver (DVM Exclude). The Hill’s brand also has taken the potato and substituted it with potato starch to decrease the carbohydrate antigenicity (Hill’s Prescription Diet Z/D Ultra Allergen Free).

The author is a firm believer that the only proper way to rule out a cutaneous adverse food reaction is by a home-prepared diet (Box 6-1). A certain percentage (not established, based on double-blinded, placebo-controlled trials) of dogs and cats respond to the novel protein or hydrolyzed diets. However, failure to respond to these diets does not rule out a cutaneous adverse food reaction. An explanation as to why the novel protein or hydrolyzed diets fail to identify dogs and cats with cutaneous adverse food reactions may include these factors:

• Sources of animal fats added to the diets may be from sources (e.g., beef or pork) other than those used for the hydrolyzed or novel protein.³

• The size of the antigen is still large enough to trigger an immunologic reaction (applies to hydrolyzed diets).

BOX 6-1 Home-Prepared Elimination Diet

We believe that your pet may have a food allergy—not an allergy to a particular brand of food, but to one of the individual ingredients. We therefore want to feed a diet that your pet has not eaten before. For this diet we will use ostrich, rabbit, goat, duck, or venison as the meat and potatoes, sweet potatoes (yams), or oats as the starch. It is very important that you adhere to the following guidelines:

1. The meat must be pure without any additives (e.g., spices, other meats [such as beef]). Be sure to mention to your butcher it must be pure meat. Make sure that if the butcher grinds the meat he uses a clean meat grinder.

2. The meat should be trimmed of any excess fat and then boiled or baked. If using duck, either skin it before cooking or poke large holes through the skin to allow the excessive fat to drain.

3. Mix the meat and starch together and let them simmer, as you would stew. Large quantities may be prepared and then refrigerated for daily feeding.

4. Occasionally we will use pinto or kidney beans instead of or in addition to meat. To prepare them, soak beans in water overnight. Throw out this water and put in fresh water. Boil until cooked—typically approximately 1 hour.

5. Feed a one-quarter meat/three-quarters starch mixture daily. If using beans, mix 50/50 with the starch. You will need to feed 1 or 2 cups for a 10-pound dog per day. For cats we will only feed the meat, no starch!

6. It is very important that your animal not be allowed to put anything in his mouth except the home-cooked diet and water. This means no vitamins, chew toys, biscuits, rawhides, or table food—nothing! (If your pet is on any medication, however, please check with us before discontinuing.) If your pet is on a chewable form (i.e., beef-flavored biscuit) of heartworm medicine, please have your referring veterinarian change it to a nonchewable form.

7. Occasionally a change in diet may cause a digestive upset—either vomiting or diarrhea. Your pet may refuse to eat the above diet. If he/she does not eat for 2 days or a digestive upset occurs, please call us for instructions before giving up. Frequently they will only have a bowel movement every other day because the food is so well digested. Please call if your pet goes more than 2 or 3 days without

a bowel movement.

8. In order to determine whether your pet has a food allergy, this diet must be strictly maintained for 4 to 12 weeks. You may not see complete relief from itching, scratching, or licking, but you should see some improvement.

9. Your pet will not be on the elimination diet for the rest of his life. Once we have established that your pet has a food allergy, we will outline procedures to deter­mine which foods cause an allergic response. When we know which pure foods cause a problem and which do not, we can choose a commercial preparation that your pet will tolerate.

10. Please schedule a reexamination/evaluation for 30 days from now. Bring your “itch” calendar with you.

Other explanations may be extrapolated from lessons learned about humans with food allergies. These explanations include the following:

• Contamination from other food prepared at the manufacturing plant by jointly used equipment or even aerosolization of antigens^20-23

• Contact with humans (or even cats or dogs) that have recently eaten the offending food²⁴

Whatever method is used for the elimination-diet trial, it should be fed for a minimum of 8 weeks in dogs and 12 weeks in cats. One possible explanation for the need for such a prolonged trial is the presence of histamine-releasing factors. Histamine-releasing factors are a heterogeneous group of cytokines generated by chronic antigenic exposure that may cause histamine release in the absence of an antigen. This release may continue for weeks after the antigen is removed.⁴

Of 265 dogs reported collectively by 12 different studies, beef, dairy products, and wheat accounted for two thirds of reactions. Reactions to corn, pork, rice, and fish were rarely reported in dogs. Of 56 cats reported collectively by 10 studies, beef, dairy products, and fish accounted for 80% of reactions.⁸