Elimination Diet Trials: Steps for Success and Common Mistakes

Food allergy (FA) is a form of allergic hypersensitivity caused by an exaggerated immune response to food antigens and is associated with either a type I (immunoglobulin E–mediated) or a type IV (cell-mediated) hypersensitivity reaction.^1,2 In dogs and cats, the clinical features of FA mimic canine atopic dermatitis and feline atopic skin syndrome (FASS), respectively.^3,4 Dogs and cats with FA frequently present with pruritus, self-induced alopecia, and erythematous skin; recurrent secondary skin and/or ear infection can also be a manifestation of FA.¹ The 2 most common gastrointestinal signs are diarrhea and vomiting.⁵ However, the absence of gastrointestinal signs does not rule out an FA.

How Common Is Food Allergy in Animals?

The prevalence of FA in dogs and cats depends on the population from which the data are extracted. In a recent review, FA made up about 18% (range, 9% to 40%) of dogs presenting with the primary complaint of pruritus.⁶ However, the prevalence increased to 20% and 29% in dogs presenting for allergic skin diseases and atopic dermatitis, respectively.⁶ Similarly, in cats presenting with pruritus or allergic skin disease, the median prevalence of FA was 17% (range, 12% to 21%) and approximately 10% (range, 5% to 13%), respectively.⁶

Because FA shares similar clinical features with canine atopic dermatitis and FASS, which have different prognoses, it is of the utmost importance that clinicians achieve a correct diagnosis. In the author’s opinion, FA has a better prognosis because it does not necessitate lifelong medical therapy and determining the appropriate diet that keeps the clinical signs in remission might be the only management needed.

Is an Elimination Diet Trial the Only Option for Diagnosing Food Allergy?

An elimination diet trial (EDT) involves strictly feeding the animal either a hydrolyzed diet or a novel-protein diet (commercially available or home cooked). The diagnosis of FA is confirmed when the pruritus resolves with feeding an elimination diet, relapses upon a diet rechallenge, and resolves again when the elimination diet is re-fed to the patient. However, there are several hurdles to performing a strict EDT. Most diets used in an EDT are more expensive than a regular commercial diet. Pet owners who choose to prepare a home-cooked novel diet may find it difficult to maintain the commitment to prepare the diet consistently. It requires a lot of effort and commitment from the owner to keep the diet strict; therefore, owner compliance may also be an issue.

The obstacles to performing a strict EDT have led to the urge to diagnose FA more simply. Serum, saliva, and hair allergy tests for FA have been commercially available for years and are often utilized as “diagnostic aids” based on their convenience. However, numerous studies have shown these tests to be unreliable in diagnosing FA in animals.^7-10

Intradermal testing (IDT) for food antigens has been evaluated in dogs in several studies.^11-13 In 1 study, neither the positive nor negative predictive values adequately predicted positive and negative reactions, respectively, for the IDT.¹² In another study, only 3 of 30 dogs that had positive IDT results for food antigens improved when fed a hypoallergenic diet.¹³ A third study reported that there was little agreement between IDT results and those of the oral food provocation test.¹¹ Taken together, IDT for food antigens does not reliably identify dogs with food allergies.

Patch testing involves applying food (e.g., raw or cooked meat) directly to the skin of the animal, securing it with hypoallergenic tape, and evaluating for a positive reaction (i.e., erythema, papules, microvesicles) after 48 hours. Two studies on the usefulness of patch testing for the diagnosis of FA in dogs showed that it has a strong negative predictive value; that is, the results can be used to determine foods to which the patient does not react.^14,15 More recently, the combination of prick and patch tests in 21 dogs with FA showed a sensitivity of 80%, specificity of 67%, positive predictive value of 67%, and negative predictive value of 80%, and the authors concluded that these tests are useful tools to aid in the selection of foods for an EDT and subsequent provocative challenge.¹⁶

An EDT therefore remains the most reliable diagnostic “test” for FA and is considered the gold standard.² Some veterinary dermatologists recommend performing a second EDT before completely ruling out an FA.

Which Diets Are Suitable for an Elimination Diet Trial?

Three categories of diet can be used in an EDT: a novel-ingredient prescription diet, a novel-ingredient home-cooked diet, or a hydrolyzed diet. A novel-ingredient prescription or home-cooked diet consists of protein and carbohydrate sources that the animal has not been exposed to. A hydrolyzed diet consists of proteins that are hydrolyzed into small peptides that reduce the chances of an allergic reaction when consumed.

The “perfect” diet for an EDT does not exist. What is more important is that the selection of the elimination diet be based on a thorough history (especially if a novel ingredient diet is selected), feasibility, and owner compliance.

Novel-Ingredient Diets

If a novel-ingredient diet is preferred, a thorough dietary history is vital to ensure that the protein and carbohydrate sources selected are truly novel to the animal. If a novel-ingredient home-cooked diet is elected, the owner must prepare a well-balanced diet that includes vitamins and minerals. A veterinary nutritionist should be consulted to obtain the best “recipe” for a well-balanced novel-ingredient home-cooked diet. The author does not recommend using a nonprescription over-the-counter (OTC) novel-ingredient diet because OTC diets may contain ingredients that are not declared.

Identifying a novel-ingredient diet is becoming more challenging due to the increased availability of OTC diets that use ingredients often used for an EDT. Additionally, owners who feed their cats or dogs human food or table scraps may inadvertently expose their pets to protein sources that cross-react with a different protein, further reducing the choices of available novel proteins to be utilized.

Hydrolyzed Diets

If the above scenarios negate the usefulness of a novel-ingredient diet in an EDT, a hydrolyzed commercial diet may be a more suitable option. These diets utilize animal or plant proteins such as poultry feathers,¹⁷ chicken liver,¹⁷ fish,¹⁸ and soybeans,¹⁹ and the peptides they contain theoretically have a much lower risk of provoking reactions when consumed, even if the animal is hypersensitive to the parent protein. However, in a systematic review, between 20% and 50% of dogs ingesting a partially hydrolyzed diet derived from the parent protein to which they were reactive exhibited a flare of clinical signs associated with FA.¹⁹ Indeed, some dogs might develop a hypersensitivity reaction to a certain hydrolyzed diet but not another from a different manufacturer.¹⁷

A Note About Over-the-Counter Commercial Diets

Because most diets intended for particular nutritional purposes are more expensive than an OTC commercial diet, pet owners often elect to feed their pets OTC diets.²⁰ However, numerous studies have shown that many OTC diets have potential contamination with common known food allergens or contain ingredients that are not declared (i.e., adulterated diet).^20-22 In a recent study, out of 29 OTC commercial dog foods tested, 65% and 41% contained undeclared chicken and pork DNA, respectively.²⁰ Although the mere presence of undeclared protein DNA may not result in a significant hypersensitivity reaction, the author prefers to avoid using nonprescription OTC diets in an EDT.

Within the past decade, several “therapeutic” diets for the management of canine atopic dermatitis have become available. These diets are fortified with antioxidants (e.g., vitamins C and E), polyphenols (e.g., turmeric), and high concentrations of essential fatty acids, which improve skin barrier function and reduce skin inflammation and pruritus.^23-26 While these diets could be a valuable adjunct in managing canine atopic dermatitis and potentially have a drug-sparing effect, they may not be suitable elimination diets as they may contain protein or carbohydrates that are not novel and could still trigger a hypersensitivity reaction.

How Can the Chances of Success With an Elimination Diet Trial Be Improved?

In the author’s opinion, the most important factor in determining the success of an EDT is client education. Owners of pets with nonseasonal pruritus need to understand that an EDT is important because it remains the most reliable “tool” to rule in or rule out FA. Theoretically, a diagnosis of FA holds a better prognosis than atopic dermatitis or FASS associated with the environment, as the latter 2 conditions are not curable and require lifelong therapy. To emphasize this, the author often explains the following to pet owners: “Your pet has the history and clinical signs of either a food allergy or environmental allergies, and I am unable to tell them apart without performing an elimination diet trial. I hope that your pet has a food allergy because that is something we can control and does not necessarily need lifelong treatments that are costly and have adverse effects. The only way to find out is to start an elimination diet trial.”

Good client education leads to increased compliance. If there is a time constraint during a clinic visit that prevents lengthy (yet important) client education, prepared handouts containing important information on the why, when, and how of an EDT are extremely helpful. The handouts should contain information on the most appropriate diet, the duration of the EDT, and the “do’s and don’ts” to keep the EDT strict. Download a client handout at go.navc.com/3Vj8vYH.

Help Clients Make the Transition

One recommendation when starting an EDT is to introduce the elimination diet gradually, not abruptly. Anecdotally, abrupt cessation of the old diet followed by abrupt replacement with a new diet may increase the risk of gastrointestinal upsets such as diarrhea or increased flatulence. If not prevented, such adverse effects might discourage pet owners from continuing with the test diet. As such, the author recommends a transition period of 5 to 7 days.

Define “Strict Adherence”

It cannot be overemphasized that pet owners need to strictly adhere to the EDT. No other pet food, human food, table scraps, treats, rawhide chews, flavored toothpaste, or daily supplements (e.g., chewable joint supplements) can be given to the pet. Flavored monthly oral preventive medications (e.g., flea, tick, and heartworm preventives) must be replaced with a nonflavored substitute or a topical formulation. The author has seen dogs that experienced an increase in pruritus when given a flavored monthly flea and tick preventive.

It is not uncommon for pet owners to assume that using a “small” amount of peanut butter or cheese or flavored pill pockets will not ruin the diet trial. Such “small” amounts may be sufficient to induce a hypersensitivity reaction and will interfere with the assessment of the EDT. If administration of medication(s) is required (e.g., oral antibiotics) during the EDT, and the owner is unable to administer it without using a flavored pill pocket (e.g., due to the pet’s temperament), the use of a suitable novel ingredient or hydrolyzed canned or wet food may be an alternative.

Account for Other Pets

Preventing the pet that is going through the EDT from having access to other pet food can be a challenge in a multipet household. Ways to mitigate this problem include feeding the pets separately or in separate, confined spaces and designating meal times instead of leaving the food out all day. Feeding all pets of the same species with the same elimination diet may increase compliance, but feasibility needs to be discussed with the owner. If such an option is favorable, it is important to ensure that the elimination diet is “age-appropriate” (i.e., puppy/kitten versus adult dog/cat) because not all hydrolyzed or novel-ingredient diets are suitable for growing animals.

Plan for Food Aversion

The palatability of the elimination diet is another hurdle that can discourage pet owners from continuing with the EDT. Pet owners often quickly give up if their pets are not consuming the test diet. This situation is even more challenging in cats because they are more sensitive to the change in the properties of a new diet (e.g., smell, texture, temperature, form).²⁷ This can lead to food aversion, which can, in turn, be detrimental because cats are more sensitive to developing hepatic lipidosis.²⁸ For dogs with food aversion, mixing dry food with wet or canned food of the same ingredients (i.e., novel or hydrolyzed) may increase the palatability of the diet. For cats, the author often recommends 2 different diets so that if the cat refuses to eat one of the diets, an alternative is readily available.

Follow Up With Clients Regularly

The pet owner needs to be reminded of the do’s and don’ts throughout the EDT. Training the front desk personnel, veterinary assistant, or veterinary nurse to perform these tasks will increase the day-to-day practice efficiency and improve time management. Other measures, such as follow-up calls, texts, or emails to encourage the client and to check for strict diet adherence, often increase client compliance. Such contact also helps to promptly identify and address issues with keeping the EDT strict.

What Is the Optimum Duration of an Elimination Diet Trial?

There is still no consensus on the optimal duration of an EDT. Some literature recommends a duration of 6 to 12 weeks,^27,29 whereas other sources state that most dogs with no improvement in the level of pruritus by the sixth week of an EDT are unlikely to have an FA.³⁰ However, a critically appraised paper found that, to diagnose FA in 80% of dogs and cats, the EDT should be a minimum of 5 and 6 weeks in dogs and cats, respectively. Increasing the duration of the EDT to 8 weeks increases the sensitivity to more than 90%.³¹

More recently, 2 studies reported that the EDT in dogs could be shortened to between 4 and 6 weeks with the addition of oral prednisolone in the initial phase.^32,33 Treatment with oral prednisolone rapidly reduces and “switches off” the inflammatory pathways, which speeds up the resolution of inflammation and chronic skin changes. The treatment protocol in these studies involved administering anti-inflammatory doses of oral prednisolone for 2 to 3 weeks. Dogs that experienced a relapse of pruritus received a second course of oral prednisolone administered for 1 week. The authors of the studies suggested that dogs that relapse more than twice are unlikely to have an FA, with the threshold of 1 relapse or less associated with a sensitivity and specificity of 95% and 100%, respectively, for the diagnosis of FA in dogs.

While this shortened EDT protocol will improve client compliance, it may not be applicable in dogs presenting with concurrent secondary bacterial and/or yeast dermatitis and/or otitis externa. Indeed, dogs with a concurrent secondary infection were not included in one of the studies described above.³³ At the time of writing, there were no published data on the usefulness of oral prednisone to shorten the EDT in cats.

In the author’s opinion, the duration of the EDT should be determined on a case-by-case basis. If there is no evidence of a secondary skin and/or ear infection, the shortened EDT protocol can be utilized to increase client compliance. If a concurrent secondary infection is present, the secondary infection needs to be treated before the shortened EDT protocol is executed; in this scenario, a progress (recheck) evaluation is required to confirm that the secondary infection has resolved completely. Otherwise, the presence of the infection will give the false impression that the elimination diet is not effective in preventing a relapse of pruritus and may lead to inaccurately ruling out an FA.

If the animal has comorbidities that do not permit the use of oral steroids (e.g., hyperadrenocorticism, diabetes mellitus), oclacitinib could be an alternative, although the sensitivity for the diagnosis of FA using oclacitinib is lower (63%).³³ The usefulness of lokivetmab (Cytopoint; Zoetis, zoetisus.com) to shorten the duration of an EDT has not yet been reported. Because the duration of the antipruritic effect in dogs receiving lokivetmab ranges between 4 and 8 weeks, the “positive” response to the EDT (i.e., the resolution of pruritus and skin lesions) within this timeframe must be interpreted cautiously, as the response may be due to the lokivetmab rather than the EDT.

If Clinical Signs Resolve, Is the Elimination Diet Trial Over?

If the animal’s pruritus and skin lesions resolve and do not relapse while the elimination diet is fed, an FA can only be confirmed if the clinical signs reappear upon reintroduction of the previous diet and improvement is seen again when the elimination diet is restarted strictly. This part of the EDT—dietary rechallenge or provocation test—is important because the improvement could be associated with medications used or changes in the environment or seasons.

During the dietary rechallenge phase, the author prefers to reintroduce the dry food (or, in some cases, home-cooked food) that the animal was consuming before the start of the EDT; if a relapse of pruritus occurs, the protein(s) or carbohydrate(s) that are listed as the ingredients should then be used individually as provocative tests after the flare has resolved. These individual provocative tests, when done sequentially, can help identify which protein(s) and/or carbohydrate(s) caused the flare. A similar dietary rechallenge protocol is then used for other foods that the animal was fed, including wet/canned food, supplements, treats, and table scraps. During this phase, pet owners should keep a logbook to document the ingredients in the diet challenge and record the outcome. This information will facilitate selecting the most appropriate long-term maintenance diet and avoiding those that cause a hypersensitivity reaction.

At the time of writing, there is no consensus on how long veterinarians should wait before ruling out FA if no signs of a relapse are observed during a diet rechallenge. In a recently published review, 234 dogs with FA were analyzed based on a total of 315 diet challenges and their outcomes.³⁴ The authors concluded that a waiting period of 14 days is needed for more than 90% of food-allergic dogs to flare. Interestingly, at least 80% of dogs developed a relapse of signs within 7 days after a diet challenge. Further supporting these data is a paper reporting that for dogs, the median time to flare after a diet challenge is 12 hours, with 98% of dogs flaring within 7 days.³⁵ The time to flare is within 7 days of a diet rechallenge in 90% of cats.³⁴

Summary

An EDT remains the most reliable tool for the diagnosis of FA in dogs and cats. For most pet owners, maintaining a strict EDT is not an easy feat, and issues such as food aversion and having a multipet household lead many to give up. To increase the success of completing the EDT, client education and follow-ups are crucial for compliance. The selection of an appropriate elimination diet is also key in determining if FA is playing a role in the clinical signs.