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Cutaneous adverse food reactions in dogs

Jon Plant, DVM, Dipl. ACVD - 11/11/2012

Cutaneous adverse food reactions in dogs

 

IntroductionKey Points

Cutaneous adverse food reaction (AFR) is an important differential diagnosis for several common dermatological presentations in dogs. The most common cutaneous presentation of AFR mimics canine atopic dermatitis (CAD) and is thought to share a common pathogenesis. Other reported cutaneous signs of canine AFR include otitis externa, pruritus, urticaria, seborrhea, vasculitis, and onychodystrophy; concurrent gastrointestinal signs may or may not be present.




How are AFRs classified?

Adverse food reactions are generally classified according to the suspected pathomechanism (Table 1) and may result from either immunologic or nonimmunologic mechanisms. The immunologic category may be subdivided into food hypersensitivity and food anaphylaxis; most cases of cutaneous AFR are presumed to be due to hypersensitivity and this article will focus on these. Non-immunologic causes of AFR include food intolerance and intoxication and these pathomechanisms are more often associated with gastrointestinal signs. Digestive enzyme deficiencies, idiosyncratic reactions to food additives, (e.g. antimicrobial preservatives, colorants, antioxidant preservatives, and emulsifying agents) and ingestion of vasoactive amines are examples of food intolerance. Intoxication may result from ingestion of bacterial or fungal toxins.


Table 1


What is the pathogenesis behind AFR?

The gastrointestinal tract has evolved to allow the body to cope with a large number of potential allergens without developing clinical hypersensitivity. Several mechanisms serve to limit the development of food allergy in normal dogs. Food allergens are usually large, water-soluble glycoproteins ranging between 10,000- 70,000 daltons. Digestion of proteins to amino acids and small peptides renders most of the ingested protein poorly immunogenic. Poorly digestible, heat-stable proteins may, therefore, be more allergenic. Proteins that remain large enough to retain allergenic epitopes encounter a mucous layer containing IgA and carbohydrate moieties that may limit allergen interaction with the microvilli. This layer may be disrupted by inflammatory and infectious diseases of the gastrointestinal tract, possibly predisposing to the development of AFR. Potential allergens must then pass through an epithelial barrier after which they encounter the gut-associated lymphoid tissue (GALT). While the GALT must mount an immune response against harmful substances and organisms, it must also produce oral tolerance to numerous food allergens through a suppressor immune response. Oral allergen tolerance is produced with the controlled exposure of food allergens to the GALT. If the mechanisms that produce oral tolerance, mediated by regulatory T-cells and lymphocyte anergy, do not function properly, sensitization may occur.

 

Although unproven in the dog, Type I (immediate, IgEmediated) hypersensitivity is believed to play a central role in food hypersensitivity. Antigen-specific IgE has been documented in some reports on spontaneously occurring food allergy in dogs, (1) but this finding has not been consistent. Type III (delayed, immune complex) and Type IV (delayed, cell-mediated) hypersensitivity reactions have also been proposed to contribute to the pathogenesis of canine AFR, but there is less evidence to support these mechanisms.

 

The concept that cutaneous AFR is a separate, distinct entity from CAD has recently been challenged (2); a large prospective study of the clinical features of CAD found only minor differences between those with food sensitivity and those without, suggesting a common pathogenesis. The term food-induced atopic dermatitis (FIAD) was proposed to describe dogs with food hypersensitivity and clinical features typical of atopic dermatitis. In humans, several oral allergens are known to cross-react with aeroallergens, resulting in clinical disease in sensitized individuals. An example is ragweed-sensitive individuals reacting to apples or melons. Few of these cases have been documented in the dog.

 

Little is known about the relative importance of various food allergens as causes of cutaneous AFR. A recent textbook (3) summarizes fifteen reports in the veterinary literature documenting 278 dogs with cutaneous AFR drawn from several continents. Beef, dairy products, and wheat were the most commonly implicated allergens followed by lamb, chicken egg, chicken and soy. Chicken serum albumin, bovine IgG, ovine IgG, and muscle phosphoglucomutase of bovine and ovine origin have been specifically identified as allergens in dogs. Multiple sensitivities are common. In one study, 64% of food allergic dogs were allergic to two or more proteins (4).




How prevalent is cutaneous AFR?

The true prevalence of cutaneous AFR in dogs is unknown. False positives or negatives are common owing to non-standardized dietary restrictionprovocation trials (DRPT). The diagnostic uncertainty is compounded by poor compliance to veterinarians’ recommendations. Of those dogs presented to dermatology referral practices, the estimated prevalence is reportedly between 7.6%-12% (5,6). Among dogs with allergic skin diseases, the prevalence is likely to be higher, with estimates ranging from 9%-36% (6,7). In humans, suspected hypersensitivity to an individual food is often not borne out when meticulously evaluated with a placebo-controlled dietary challenge.




Which dog breeds are predisposed?

Strong epidemiological data is lacking but certain dog breeds may be predisposed to AFR, including the American cocker spaniel, boxer, Chinese sharpei, collie, dachshund, Dalmatian, English springer spaniel, German shepherd, golden retriever, Lhasa apso, miniature schnauzer, poodle, pug, Rhodesian ridgeback, and West Highland white terrier (6,7).


Figure 1 and 2

What are the clinical features?

AFR may occur at almost any age; documented cases note dogs between four months and 14 years old as being affected (3). Children are more frequently diagnosed with food hypersensitivity than adults and there are some reports suggesting that the prevalence of cutaneous AFR may be higher in puppies than in adult dogs (8). The cutaneous signs can vary, with FIAD, pruritus, and otitis externa being the most common.



Food-induced atopic dermatitis

The most common presentation of cutaneous AFR is nearly identical to CAD triggered by environmental allergens, or non-food induced atopic dermatitis (NFIAD). Common features can include (i) affected front feet and/or pinnae, (ii) < 3 years old at onset, (iii) pruritus that is responsive to corticosteroids, (iv) recurrent or chronic yeast dermatitis, (v) living indoors, (vi) non-affected pinnal margins, and/or (vii) non-affected lumbosacral region. In a study of 843 atopic dogs, minor differences were found between FIAD and NFIAD groups (2). Compared to the NFIAD group, the FIAD group displayed significant changes in seasonality of signs (decreased), gastrointestinal disturbance (increased), eyelid dermatitis (decreased), pruritus without cutaneous lesions (decreased), and response of pruritus to glucocorticoids (decreased). In an individual dog these differences are not sufficient to differentiate between FIAD and NFIAD and a DRPT is necessary; a partial response suggests both food and environmental triggers.

 

In addition to the front feet (Figure 1) and pinnae, the hind feet, axillae, and abdomen are most affected in FIAD. Less frequently affected regions include flexural surfaces of the elbow, front limbs, rear limbs, lips, face, chest, and genitalia (2). Secondary bacterial and yeast infections are common and may spread.



Pruritus

Pruritus sine materia (pruritus without visible signs) precedes the development of skin lesions in most affected dogs. In the aforementioned study (2) 47% of dogs diagnosed with FIAD exhibited pruritus before skin lesions.



Otitis

By some estimates (8) 25% of dogs with cutaneous AFR exhibit otitis alone (Figure 2); this is usually bilateral but can be unilateral. Dogs are often presented for the secondary infections that develop subsequent to the inflammation. Malassezia pachydermatis is often the predominant organism early in the course of otitis externa, while Staphylococcus spp. and Gramnegative organism infections often develop in chronically affected ears. A DRPT is an important consideration in determining the underlying cause of chronic or recurrent otitis externa.



Recurrent bacterial folliculitis

A less common presentation of cutaneous AFR is recurrent bacterial folliculitis (Figure 3), usually caused by Staphylococcus pseudintermedius. In contrast to FIAD, which is often accompanied by secondary pyoderma, pruritus is not a primary feature of this presentation. Dogs with recurrent bacterial folliculitis due to cutaneous AFR may be non-pruritic, or the pruritus may resolve with appropriate antimicrobial therapy alone, only to recur if the dietary sensitivity is not addressed.



Seborrhea

AFR in dogs may present as dry or oily forms of seborrhea. Generalized scaling, alopecia, lichenification, erythema and hyperpigmentation may develop. Secondary bacterial and yeast infections are common, due to the disruption of the normal keratinisation process.



Urticaria

Hives are an uncommon cutaneous manifestation of AFR. Urticarial reactions may be localized to a body region or generalized. Hives result in clusters of erect hairs, most easily recognized in short-haired dogs. Pruritus with this form of cutaneous AFR is variable.



Vasculitis

Cutaneous AFR is one of many possible causes of cutaneous vasculitis. Erythematous macules, ulcers and crusts are commonly observed lesions. Affected areas often include the concave pinnal surface, pinnal margins (Figure 4), and foot pads, but any region of the body may be affected. Vasculitis can be recognized clinically by the failure to blanch with pressure, indicating extravascular hemorrhage.



Symmetric lupoid onychodystrophy

An apparently rare manifestation of cutaneous AFR is symmetric lupoid onychodystrophy (9). Multiple claws on all feet develop abnormally and may become soft (onychomalacia), split (onychoschizzia and onychorhexis), and slough (onychomadesis). Several dogs are reported to have responded either partially or completely to dietary restriction trials.



Erythema multiforme

Another unusual presentation of cutaneous AFR is erythema multiforme, characterized by target-shaped or polycyclic erythematosus macules that tend to heal centrally while spreading peripherally. Histopathology of erythema multiforme is typified by isolated apoptosis of keratinocytes. Cutaneous AFR is one of many causes of erythema multiforme.


Figure 3 and 4


Do affected dogs show gastrointestinal signs?

Dogs with cutaneous AFR may have concurrent gastrointestinal signs, including vomiting, diarrhea, loose stools, flatulence, and increased frequency of defecation (3.1 times per day in dogs with cutaneous AFR versus 2.2 times per day in dogs pruritic due to other diseases) (10). The prevalence of gastrointestinal signs among dogs with cutaneous AFR varies between reports, ranging from 10%-31% (2,6).




How do I diagnose cutaneous AFR?

The DRPT remains the only method to diagnose cutaneous AFR in the dog. Allergen-specific IgE testing and intradermal testing, although available, fail to demonstrate reliability and cannot be recommended for diagnosis (6). To perform a DRPT, a diet is identified based on the dog’s dietary history. The pet is first transitioned to the test diet, then it is fed strictly for a period of time, and finally it is challenged with the previous diet or individual dietary ingredients while observing for an exacerbation of signs (Table 2). When possible, flavored medications should be replaced with non-flavored alternatives. While simple in concept, carrying out a strictly controlled DRPT is challenging for many pet owners. Most dogs with cutaneous AFR will have at least a partial response to an appropriate diet in eight weeks; a percentage may require longer (8). If a positive response is observed, many owners are reluctant to undertake the provocation portion of the trial. If no significant response is seen, then cutaneous AFR is unlikely. Common pitfalls include an uninformed choice of test diet, willfully poor adherence to the diet by a family member, and dietary indiscretions by the dog. During the initial weeks, it may be necessary and humane to treat for pyoderma, Malassezia dermatitis, otitis externa, and to provide temporary antipruritic medications.

 

 

Gaining the owner’s commitment to adhere to the DRPT is crucial, but can be influenced by many factors. One author describes the use of a Venn diagram to emphasize the relationship between atopic dermatitis and food allergy when educating pet owners presented with the prospect of conducting a DRPT (5); this approach reduced the number of clients prematurely discontinuing the trial from 52% to 27%. As part of the client education, he emphasized the relative ease with which cutaneous AFR can be managed long term, compared to CAD.


Table 2

 


How do I select a test diet?

The first step in selecting a diet for a DRPT is to gather a complete dietary history, taking particular note of protein sources that have been fed. Diets may have been fed for years before signs of cutaneous AFR develop. This may seem counterintuitive to many dog owners. If a detailed dietary history is available, a novel protein diet may be selected. When a suitable dietary history is unavailable, as may be the case for a dog adopted as an adult, a hydrolyzed protein diet may be a better choice.



Novel protein diets

The protein used in commercially-available novel protein diets vary in different parts of the world, according to availability and social convention. They can include venison, lamb, rabbit, duck, various fish, moose, goat, ostrich, wild boar, and emu, among others. Care should be taken to select diets derived from a single major protein source whenever possible; complete ingredient information may not be displayed, depending on labeling requirements in different countries. In some instances, protein sources not listed on the label can be detected with laboratory techniques. For instance, analysis of over-the-counter (OTC) venison diets found unlisted proteins (soy, poultry, or beef) in three out of four foodstuffs examined (11). Cross contamination is possible during many phases of the manufacturing and packaging process. One manufacturer may produce contract pet foods for dozens of companies using hundreds of different recipes.

 

It is advisable to select a protein source as taxonomically distinct from previous diets as possible. Cross-reactivity among meats from various sources has not been studied yet in dogs (6). Carbohydrate sources are less often described as causes of cutaneous AFR, but the ideal diet includes a novel carbohydrate source as well.



Hydrolyzed protein diets

As previously discussed, food allergens are typically large glycoproteins. In manufacturing hydrolyzed diet ingredients, proteins are reduced in size below 10,000 daltons, theoretically reducing their allergenicity. Several companies produce hydrolyzed chicken or soy-based diets for the market place. Studies have found that hydrolyzed diets are tolerated by most, but not all, dogs with food sensitivity to the native protein (13,14). A systematic review of 11 studies that reported on hydrolyzed protein diets concluded that they should be avoided when the native protein is suspected as an allergen, since occasional dogs still display signs of cutaneous AFR when fed the hydrolyzed diets derived from known allergens (15).



Home-prepared diets

If an owner is willing to prepare a well-balanced, single-protein source diet for several weeks, homecooked diets are an alternative. Freshly preparing food offers the advantage of avoiding food additives; note AFR due to food additives is rarely documented. Many moist pet foods are free of additives. If owners choose to home cook, a balanced recipe formulated by a veterinary nutritionist should be carefully followed (3).

 

The idea of feeding raw food diets appeals to some. There is no evidence that raw foods are superior to cooked foods as a restriction diet; in fact, heating proteins can render them less allergenic in humans. In addition to the above formulation considerations, rawfood diets place the dog and owner at increased risk of exposure to pathogenic Salmonella spp., E. coli, and other microorganisms (12).



Provocative challenge

Dogs that respond to the restricted diet can be challenged with either their previous diet, or its individual ingredients, treats, or flavored medications. Unless this step is taken, the diagnosis of cutaneous AFR can only be made tentatively, as other influences may have resulted in the improvement. Dogs with cutaneous AFR, once re-exposed to their offending allergen(s), may display an exacerbation of signs (3). From a practical point of view, re-introducing one individual ingredient per week is recommended.




Conclusion

Cutaneous AFR is common in the dog and the most frequent presentation is indistinguishable from CAD based on clinical features alone. An 8-12 week DRPT utilizing novel-protein or hydrolyzed-protein diets is necessary for diagnosis. Once the offending food or ingredients have been identified, the novel-protein or hydrolyzed diet may prove suitable as a maintenance diet, or the owner may prefer to experiment with new foods. Assuming the allergens have been identified and can be avoided, the prognosis for dogs with cutaneous AFR is excellent. 

 

This article was kindly provided by Royal Canin, makers of a range of veterinary hypoallergenic diets for dogs and cats. For the full range please visit www.RoyalCanin.co.uk or speak to your Veterinary Business Manager:

 

REFERENCES

1. Ishida R, Masuda K, Sakaguchi M, et al. Antigen-specific histamine release in dogs with food hypersensitivity. J Vet Med Sci 2003;65:435-438.

2. Favrot C, Steffan J, Seewald W, et al. A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis. Vet Dermatol 2010;21:23-31.

3. Roudebush P, Guilford WG, Jackson HA. Adverse reactions to foods. In: Hand MS, Thatcher CD, Remillard RL, Roudebush P, Novotny BJ, eds. Small animal clinical nutrition. 5th ed. Topeka: Mark Morris Institute, 2010;609- 635.

4. Jeffers JG, Meyer EK, Sosis EJ. Responses of dogs with food allergies to single-ingredient dietary provocation. J Am Vet Med Assoc 1996;209:608-611.

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6. Gaschen FP, Merchant SR. Adverse food reactions in dogs and cats. Vet Clin North Am Small Anim Pract 2011;41:361-379.

7. Picco F, Zini E, Nett C, et al. A prospective study on canine atopic dermatitis and food-induced allergic dermatitis in Switzerland. Vet Dermatol 2008;19:150-155.

8. Rosser EJ. Diagnosis of food allergy in dogs. J Am Vet Med Assoc 1993;203:259-262.

9. Mueller RS, Rosychuk RA, Jonas LD. A retrospective study regarding the treatment of lupoid onychodystrophy in 30 dogs and literature review. J Am Anim Hosp Assoc 2003;39:139-150.

10. Loeffler A, Lloyd DH, Bond R, et al. Dietary trials with a commercial chicken hydrolysate diet in 63 pruritic dogs. Vet Rec 2004;154:519-522.

11. Raditic DM, Remillard RL, Tater KC. ELISA testing for common food antigens in four dry dog foods used in dietary elimination trials. J Anim Physiol Anim Nutr 2011;95:90-97.

12. Michel KE. Unconventional diets for dogs and cats. Vet Clin North Am Small Anim Pract 2006;36:1269-1281.

13. Ricci R, Hammerberg B, Paps J, et al. A comparison of the clinical manifestations of feeding whole and hydrolysed chicken to dogs with hypersensitivity to the native protein. Vet Dermatol 2010;21:358-366.

14. Jackson HA, Jackson MW, Coblentz L, et al. Evaluation of the clinical and allergen specific serum immunoglobulin E responses to oral challenge with cornstarch, corn, soy and a soy hydrolysate diet in dogs with spontaneous food allergy. Vet Dermatol 2003;14:181-187.

15. Olivry T, Bizikova P. A systematic review of the evidence of reduced allergenicity and clinical benefit of food hydrolysates in dogs with cutaneous adverse food reactions. Vet Dermatol 2010;21:32-41.

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