Introduction

The skin has complex nutritional requirements. Adverse food reactions (AFRs) have been recognised for many years but the relationship between diet and skin disease involves more than allergies. This lecture will discuss current views from the perspective of a dermatologist and a nutritionist.

How Might Diet Affect the Skin?

Potential factors affecting the skin include:

• Food intolerance (e.g., lactose)
• Toxic or pharmacological reactions
• Type 1, 2, 3, 4 or mixed hypersensitivity reactions
• Novel proteins
• Hydrolysed proteins
• Increased digestibility
• Probiotics and prebiotics
• Altered fat content and essential fatty acids
• Changed or reduced additives
• Isoflavones and other immunomodulators

These are not mutually exclusive and clinicians should therefore carefully evaluate each patient before deciding on the most suitable diet for diagnosis of AFRs and management of skin conditions. The needs of other body systems and weight management must also be considered.

AFRs and Food-Induced Atopic Dermatitis

We now differentiate cutaneous AFRs from food-induced atopic dermatitis (FIAD). There is a complete response to diet restriction-provocation in AFRs. In FIAD there is a partial response to diet restriction-provocation - foods can be a trigger for AD but sensitisation to environmental allergens, a poor skin barrier, and altered skin inflammation also contribute.

Clinical Signs of AFRs and FIAD

Most start between 1 and 4 years of age, with 30–50% starting <1 year (compared to 16% of non-food associated AD). The foods may have been fed for 2 years or more. Clinical signs are non-seasonal, with seasonal flares associated with concurrent environmental allergies. Skin and GIT signs are seen in 30–60% of dogs and 10–30% of cats. Head and neck dermatitis is particularly associated with feline AFRs. Oral allergy syndrome (IgE mediated pruritus and swelling of the lips and oral cavity) has been recognised in dogs sensitised to Cry j 3 (Japanese cedar; Cryptomeria japonica) that cross-reacts with tomato but foods may also stimulate acute sneezing and conjunctivitis.

Food Allergens

Any protein can be an allergen. Most dogs react to more than one (mean 2.4), although the data is limited by inconsistent provocation studies.

International Committee on Allergic Diseases in Animals: Position paper on food allergens

Most allergens are 10–70 kD glycoproteins. Specific allergens in dogs include bovine serum albumin, muscle phosphoglucomutase, and bovine and ovine IgG.

Cross-Reaction Between Food Allergens

There is significant co-sensitisation and/or cross-reaction among food allergens, which is more frequent and stronger among related allergens. For example, goat, bison, buffalo, water buffalo and antelope are ‘exotic’ but would not be novel compared to lamb or beef. Cross reactions in dogs include beef & lamb; and chicken, duck & turkey. Mammalian and avian foods don’t cross-react.

Choosing a Diet for a Diet Trial

Diets can be home cooked or a commercially prepared dried or tinned foods. However, identifying novel foods is hard. Owners may not remember or be aware of what’s been fed, and may not be aware of all the ingredients in foods, treats and supplements. Recipes vary and some ingredients may not be listed. Undeclared proteins have been found in up to 80% of tested foods.

Food Allergen Serology and Patch Testing

Serology tests are widely used but only two are validated. The Avacta Sensitest® IgE ELISA has a positive predictive value (PPV) of ∼30% and negative predictive value (NPV) was ∼80% - i.e., for every three dogs with a positive IgE titre only one is allergic to that food, and for every five negative dogs four are not sensitised to that allergen and it would be suitable for a food trial. The Cynodial® test uses Western blots of whole diets rather than individual proteins. The PPV is ∼79% and the NPV is ∼78%. Therefore these tests should not be used to diagnose a food allergy, but may identify suitable ingredients for diet trials.

Patch Testing

Patch testing with food extracts is more accurate - the very high NPVs make reactions highly unlikely. However, low PPVs limit the significance of positive tests. Carbohydrates are less reliable than proteins and the results from commercial foods are poor. They are also difficult and time consuming to perform.

Home Cooked Diet Trials

These are regarded as the ‘gold standard’. However, it is often difficult to find suitable cost-effective and available foods. These are also difficult and time consuming to prepare and are not balanced for long-term feeding (or in animals with specific nutritional requirements). Minced and processed meat should be avoided, as the contents can’t be guaranteed.

Single Protein Diets

There is now a variety of single protein, single carbohydrate complete dried and tinned diets. They are often marketed as ‘hypoallergenic’ but are only so if the animal does not react to any of the ingredients. These are easy to prepare, balanced and palatable but the exact ingredients may be unknown (e.g., colourings, flavourings, preservatives, and other carbohydrates, proteins and fats) and it may not be possible to find a diet that contains a novel ingredients.

Hydrolysed Foods

Hydrolysis reduces the proteins to <5–10 KDa, theoretically rendering them non-immunogenic. However, partial hydrolysation leaves larger (potentially allergenic) fragments. Contamination during manufacture and inclusion of fats and other nutrients could also be a problem. Canine IgE has been shown to bind to maize starch synthase 1 and other proteins (15–60 kD) in three hydrolysed foods (Royal Canin Anallergenic, Purina HA and Hill’s z/d Low Allergen). The degree of hydrolysis is important - up to 20% of dogs sensitized to chicken and soy reacted to a partially hydrolysed diet (Royal Canin Hypoallergenic). Where possible, therefore, try to avoid source proteins to which an animal has been exposed. In contrast, ELISA inhibition is much less with a fully hydrolysed diet (Royal Canin Anallergenic) than with non­ or partially-hydrolysed chicken meal and comparable to negative controls. In addition, this diet provoked much fewer and milder reactions in chicken-sensitized dogs than Hills z/d (chicken liver hydrolysate) and was comparable to home-cooked novel diets in a trial of 69 dogs with pruritus.

Palatability varies, so it’s worth trying different foods (e.g., Royal Canin Anallergenic [chicken feathers & maize starch], Purina HA [soy & maize starch] and Farmina UltraHypo [fish & rice starch]) and/or adding some novel cooked foods to improve the taste.

Grains and Glutens

Owners are often very concerned over grains and glutens. Maize, rice and wheat proteins are highly digestible. Allergies to wheat glutens occur but gluten specific reactions are rare (most commonly in Irish Setters and Border Terriers).

Managing Food Trials

The keys to a successful diet trial are communication and support. Important points include: explaining the need for the trial and the process; managing expectations; getting family and friends on board; and explaining how strict the trial must be. Diaries or treatment logs are very useful.

Things to watch out for include: flavoured medications, toothpaste, treats and scraps, hidden ingredients, eating faeces, discarded and dropped food, and ‘empty’ bowls. It is important to provide a treat options - e.g., bake the kibble or tinned food into treats, make liver cakes, and dry exotic meats (e.g., kangaroo or ostrich) into jerky.

Compliance can be helped by allowing short courses of glucocorticoids or oclacitinib for 3–5 days at the owners’ discretion to manage pruritus. It’s also important to manage infections and ectoparasites during food trials.

Length of the Trial and Food Challenge

The optimum length is 8 weeks. Using faecal consistency and pruritus scores can help follow up - GIT signs respond quickly, followed by acute and then chronic skin lesions. If the GIT signs haven’t resolved in 2–3 weeks consider compliance problems or another food. Resolution of the GIT signs can encourage owners to keep going.

A food challenge will show cause and effect. Animals with AFRs should relapse within 14 days. However, fear of relapse can make owners reluctant to challenge. It is helpful to identify the offending foods using sequential challenges. However, many owners just test a few foods and treats.

Food Trials in Cats

Feline food trials are more difficult. Cats may prefer variety and there is a risk of hepatic lipidosis if they are starved for more than a few days. Many cats will also access food from other animals in the home or outdoors, and it can be difficult to keep an outdoor cat indoors for a long period. Most cats won’t accept carbohydrate so all protein diets may be necessary. Feline diets must also have adequate amounts of taurine and essential fatty acids, although simple home-cooked diets for 6–8 weeks should be fine for healthy adults.