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Diagnosing cutaneous adverse food reactions

Are hydrolysed diets a gold standard approach to diagnosing cutaneous adverse food reactions?

13 September 2019, at 9:00am

Dermatological cases are common in small animal practice, accounting for around 20 percent of all consultations (Hill et al., 2006). Cutaneous adverse food reaction (CAFR) is recognised as a potential cause of dermatological signs, affecting around 5 percent of cats and dogs with skin disease (Olivry and Mueller, 2017). CAFR is an important differential in any pruritic patient that is free of parasites and infection.

Mueller et al. (2016) evaluated food allergen sources in cats and dogs. In cats with CAFR, the most common allergens are beef, fish and chicken. For dogs, beef, dairy and chicken are the most frequently reported allergens. Olivry and Bexley (2018) recognised that cats and dogs with CAFR are likely to be suffering from true food allergies with an immunologic basis as opposed to food intolerances.

Diagnosing CAFR

There are a number of tests available for diagnosing CAFR. These include serum testing for food antigen-specific IgE and IgG, intradermal testing with food antigens and hair and saliva testing. It is widely recognised in the literature that no commercially available laboratory test can reliably diagnose CAFR in cats and dogs.

Patch testing, whilst not suitable for diagnosing CAFR, can be a useful tool in identifying suitable ingredients for an elimination diet trial (Bethlehem et al., 2012). However, keeping patch test chambers securely in place can be difficult and so it is not commonly done in small animal practice.

Mueller and Olivry (2017) have identified lymphocyte proliferation tests as having a higher accuracy in diagnosing CAFR compared with other in vitro tests. Due to the difficulty of conducting this test, it is usually performed in highly specialised research laboratories and is therefore not commercially available.

Given the unreliability of laboratory tests, the gold standard approach for diagnosing CAFR in pets is to perform an elimination diet trial (Ricci et al., 2013; Mueller and Olivry, 2017).

Choosing a diet

The selected diet for an elimination diet trial can be either home prepared or one that is commercially available. Choosing suitable ingredients can be challenging because of the complexity of today’s pet food market and the difficulties in obtaining a complete feeding history from the pet owner.

Home-prepared novel protein diets

For feeding a novel protein diet, a single protein source that the animal has not previously been exposed to should be selected. A home-prepared diet allows the owner to become very involved in this process, but these diets can be time consuming, expensive and, importantly, are not nutritionally complete and balanced unless formulated
under the direction of a board-certified nutritionist (Verlinden et al., 2006). Chandler (2018) notes that some nutrients that are especially important for skin health, such as zinc and essential fatty acids, are often deficient in homeprepared diets.

Commercial novel protein diets

When choosing a commercially available novel protein diet for the patient, the veterinary surgeon and pet owner are likely to rely on the pet food label to identify and avoid any potential allergens. Unfortunately, the mislabelling of pet foods is common, even in products proposed for elimination diet trials.

Olivry and Mueller (2018) found that up to 83 percent of tested pet foods were mislabelled, with unexpected additional ingredients occurring more frequently than missing
ingredients. With the exception of one instance, diets containing hydrolysed proteins were not found to contain any additional unexpected protein sources.

A potential concern with a novel protein diet – whether homemade or commercial – is cross-reaction among food allergens. Bexley et al. (2018) demonstrated IgE crossreactivity between chicken and fish meats in dogs, and points out that CAFR could be mistakenly ruled out if a patient fails to respond to a diet containing crossreacting allergens.

Hydrolysed protein diets

Diets containing hydrolysed proteins allow veterinary surgeons to offer a complete and balanced diet whilst alleviating the need to find novel proteins and also reducing problems associated with cross-reacting allergens (Olivry et al., 2017).

Clinical signs of AFR result from mast cell degranulation that occurs in response to the cross-linking of two IgE receptors at the cell surface (Figure 1). The purpose of hydrolysis is to disrupt the protein structure, thereby reducing the molecular weight of the original protein. The degree of hydrolysis is important because the molecules created should be too small to allow for cross-linking (Figure 2).

The most common allergens are sized from 15 to 40kDa, although smaller molecules can cause a reaction (Lesponne et al., 2018). Reducing the size of the peptides to smaller than 1kDa would give the best chance of eliminating any allergic response.

Just 13 years ago, it was believed that this degree of hydrolysis was unrealistic for pet food manufacturers due to the expense. However, recently pet food manufacturers have successfully produced such products. Extensively hydrolysed poultry feather protein is not recognised as an allergen by cats and dogs with a known sensitivity to poultry (Bizikova and Olivry, 2016; Olivry et al., 2017).

The digestibility of a hydrolysed protein is considered to be better than that of the original intact protein (Cave, 2006). These hydrolysed protein diets are also manufactured under strict quality control measures to prevent any contamination by unexpected ingredients. The palatability is generally good and they will often contain added support for a healthy skin barrier, making hydrolysed protein diets the gold standard choice for elimination diet trials.

Elimination diet trial

In order to perform a successful elimination diet trial, full dedication from the pet owner is required: the chosen diet must be fed exclusively for the duration of the trial. To make a diagnosis of CAFR in more than 90 percent of cats and dogs, diet trials should last eight weeks (Olivry et al., 2015). A food transition period of five to seven days is recommended at the start of the trial for optimal palatability and digestibility.

It is important to maintain regular contact with the owner to monitor patient progress and owner compliance. Consideration should be given to treats, food given with medication, dropped human food, toothpaste and flavoured medications as these could disrupt the trial (Chandler, 2018).

If clinical signs do not improve during the elimination diet trial, CAFR can be ruled out and other causes such as atopic dermatitis can be suspected (Ricci et al., 2013).

Provocation tests

Following resolution of clinical signs during the elimination diet trial, the reintroduction of the pet’s original diet will result in the return of symptoms in animals with CAFR. Owners may be unwilling to perform this challenge test after a reduction in clinical signs but it is an important step in confirming the diagnosis.

To identify the ingredients responsible for the pet’s clinical signs, individual protein sources can be added to the elimination diet. It is important that the cat or dog is stable
on the diet with maximum reduction of clinical signs prior to this. One ingredient can be added for a period of one to two weeks and if no clinical signs are detected, this can be changed for a second ingredient with the cycle repeating until all possible sources from the previous diet have been tested (Verlinden et al., 2006).

Summary

In any pruritic cat or dog that is free of parasites and infection, CAFR should be an important differential. The only reliable method of diagnosis is to perform an elimination
diet trial with subsequent provocation tests. The choice of diet is extremely important with extensively hydrolysed protein diets being gold standard.

The principle of managing these patients long term is strict avoidance of any offending food allergens. Hydrolysed protein diets are a convenient and balanced option not just for the elimination diet trial but also for long-term feeding.

References
Author Year Title
Bethlehem, S., Bexley, J., and Mueller, R. S. 2012 Patch testing and allergen-specific serum IgE antibodies in the diagnosis of canine adverse food reactions. Veterinary Immunology and Immunopathology 145 (3-4): 582-589
Bexley, J., Kingswell, N., and Olivry, T. 2018 Serum IgE cross-reactivity between fish and chicken meats in dogs. Veterinary Dermatology 30: 25-e8
Bizikova, P., and Olivry, T. 2016 A randomised, double-blinded crossover trial testing the benefit of two hydrolysed poultry-based commercial diets for dogs with spontaneous pruritic chicken allergy. Veterinary Dermatology 27 (4): 289-e70
Bryan, J., and Frank, L. A. 2010 Food allergy in the cat: a diagnosis by elimination.Journal of Feline Medicine and Surgery 12 (11): 861-866
Chandler, M. 2018 Dietary therapy for dermatological disorders in companion animals. Veterinary Times 48 (28)
Hill, P. B., Lo, A., Eden, C. A. N., et al. 2006 Survey of the prevalence, diagnosis and treatment of dermatological conditions in small animals in general practice. The Veterinary Record 158: 533-539
Johansen, C., Mariani, C., and Mueller, R. S. 2017 Evaluation of canine adverse food reactions by patch testing with single proteins, carbohydrates and commercial foods. Veterinary Dermatology 28 (5): 473-e109
Lesponne, I., Naar, J., Planchon, S., et al 2018 DNA and protein analyses to confirm the absence of cross-contamination and support the clinical reliability of extensively hydrolysed diets for adverse food reaction –pets. Veterinary Science 5 (3): 63
Mueller, R. S., Olivry, T., and Prélaud, P. 2016 Critically appraised topic on adverse food reactions of companion animals (2): common food allergen sources in dogs and cats. BMC Veterinary Research 12 (9)
Mueller, R. S., and Olivry, T. 2017 Critically appraised topic on adverse food reactions of companion animals (4): can we diagnose adverse food reactions in dogs and cats with in vivo or in vitro tests? BMC Veterinary Research 13 (275)
Olivry, T., Mueller, R. S., and Prélaud, P. 2015 Critically appraised topic on adverse food reactions of companion animals (1): duration of elimination diets. BMC Veterinary Research 11 (225)
Olivry, T., Bexley, J., and Mougeot, I. 2017 Extensive protein hydrolysation is indispensable to prevent IgE-mediated poultry allergen recognition in dogs and cats. BMC Veterinary Research 13 (251)
Olivry, T. and Mueller, R. S. 2017 Critically appraised topic on adverse food reactions of companion animals (3): Prevalence of cutaneous adverse food reactions in dogs and cats. BMC Veterinary Research 13 (51)
Olivry, T. and Bexley, J. 2018 Cornstarch is less allergenic than corn flour in dogs and cats previously sensitised to corn. BMC Veterinary Research 14 (207)
Olivry, T. and Mueller, R. S. 2018 Critically appraised topic on adverse food reactions of companion animals (5): discrepancies between ingredients and labelling in commercial pet foods. BMC Veterinary Research 14 (24)
Ricci, R., Granato, A., Vascellari, M., et al. 2013 Identification of undeclared sources of animal origin in canine dry foods used in dietary elimination trials. Journal of Animal Physiology and Animal Nutrition 97: 32-38
Verlinden, A., Hesta, M., Millet, S., et al. 2006 Food allergy in dogs and cats: a review. Critical Reviews in Food Science and Nutrition 46 (3): 259-273

Rachael Bufton, BSc (Hons), GradDipVN, RVN, graduated from the University of Bristol in 2010 with a degree in veterinary nursing and practice administration, and later gained a graduate diploma in professional and clinical veterinary nursing from the RVC. Rachael is now Veterinary Business Manager at Royal Canin

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