Diet can have a profound effect on skin diseases for two broad reasons - it can be the primary cause of the disease, from hypersensitivity to deficiency, and it can be used to have a therapeutic effect, independent of whether food hypersensitivity exists. Nonetheless, the most common reason for considering the diet of a patient with skin disease is as a possible cause of hypersensitivity. However, although diagnosing food hypersensitivity is conceptually simple, it is frequently difficult.
The most common reasons for failure to diagnose a true food hypersensitivity are:
1. Inappropriate selection of elimination diet
2. Client noncompliance
3. Inadequate duration
4. Failure to manage secondary bacterial pyoderma or Malassezia dermatitis
5. Appropriate food elimination trials
Simply put, the dietary experiences of the individual patient define the novelty of the diet, nothing else, including the manufacturer. If the animal has not eaten that protein before, it is novel. Although great care should be taken to identify as many of the previously eaten protein sources as possible, the majority of food hypersensitivities are to the dietary staples. Thus, avoiding the most commonly eaten proteins will usually, though not always, lead to success. Care should be taken when assessing the protein content of a diet, to consider all major ingredients as potential protein sources, including the fat and carbohydrate sources. Ingredient splitting may lead to a significant amount of the protein content being supplied by several different components. Select diets have a small number of main ingredients.
Home-prepared diets (HPDs) have the principle advantage of flexibility. Patients for which HPDs are recommended often have more than one specific nutritional consideration beyond antigenic novelty. This may include the need for fat restriction, a history of urolithiasis, chronic kidney disease, or most commonly, client or animal preference. However, HPDs are not necessarily more palatable, and if formulated to be complete and balanced, they will often have 6 or more separate ingredients. An unpublished phone survey of clients of the Nutrition Consulting Service of the University of California, Davis, found that within weeks of starting a prescribed HPD, the great majority of clients either modify, add commercial food, or abandon the diet completely.
Initial selection of a commercial hydrolyzed protein diet for a particular patient should probably still be based upon the protein source. With the possible exception of the Royal Canin Anallergenic diet, the currently available diets are insufficiently hydrolyzed to guarantee the complete absence of any allergens. Therefore, it is prudent to select a diet that does not contain a protein source that the patient is known or suspected to be sensitized to. Secondary consideration should be given to the sources of carbohydrate and lipid, as sources of potential protein allergens, and (unproven) as sources of carbohydrate or lipid antigens.
The question when a patient fails a food trial is always "was that a sufficient test to completely exclude food hypersensitivity?" That question is often hard to answer. Improvement of the key clinical signs may take a long time, and food elimination trials should extend to 10 weeks. However, the duration required is probably more determined by client compliance and secondary complications, such as pyoderma, than the true time it takes for a hypersensitivity reaction to resolve. Thus, the greater the emphasis on compliance and care to eliminate secondary microbial overgrowth, the greater the chance of conducting diagnostic elimination trials.
Both the amount and type of dietary fat has profound effects on the skin.1,2 The polyunsaturated fatty acids determined to be essential for normal skin development and maintenance are defined as the essential fatty acids (EFAs). In animals fed an EFA-deficient diet, the skin becomes scaly and inelastic, with generalised alopecia, and, histologically, the epidermis becomes noticeably thicker.3 Barrier function is disturbed, leading to increased absorption of allergens and microbial compounds, and increased evaporative water loss that leads to a relative polydipsia.
The dietary content of PUFA determines the proportions of the 20 carbon n-6 fatty acids arachidonic acid (AA), dihomo-γ-linolenic acid (DGLA), and the n-3 fatty acid eicosapentanoic acid (EPA) within the phospholipids cell membranes of leukocytes and other cell types. Incorporation of EPA in place of AA in phospholipid membranes alters the physical and structural properties of the cell membranes in lymphocytes. In particular, the assembly of lipid rafts, within which most cell surface receptors are localised, is altered. In T-lymphocytes in vitro, this has the effect of decreasing signal transduction through the T cell receptor and thus depresses T-lymphocyte activation.4 When AA is used as the substrate, 2-series prostaglandins and thromboxane (e.g., PGE2 and TXA2), and 4-series leukotrienes (e.g., LTB4) are produced. Those derived from EPA are the 3-series prostaglandins and thromboxane (e.g., PGE3 and TXA3), and the 5-series leukotrienes (e.g., LTB4). EPA and AA are competitive substrates for cyclooxygenase (COX) and lipoxygenase (LOX). EPA is a less efficient substrate for COX, resulting in reduced prostaglandin production. In contrast, EPA is the preferred substrate for LOX, and when both AA and EPA are available, the production of 5-series leukotrienes predominate. Feeding diets that are enriched in the n-3 PUFA EPA can reduce AA-derived eicosanoids by up to 75%. The conversion of the 18-carbon alpha linolenic acid (α-LA) into EPA does not occur to any significant degree in cats, and is very limited in dogs. Therefore, the effect of enriching a diet in α-LA will likely have little effect on immunity in either species.
Linoleic acid (LA C18:2 n-6) has a specific and essential function in maintaining the integrity of the epidermal barrier against water loss, and antigen absorption.5 LA is preferentially incorporated into complex lipids secreted by epidermal cells, and in dietary deficiency, oleic acid is incorporated (C18:1 n-9). The decreased fluidity of oleic acid-based ceramides leads to a dull, greasy, yet dry appearing coat, with clumping of exfoliated cells (scale). The role of the n-3 PUFA ALA (C18:3 n-3) is less clear, since little is incorporated into ceramide in rats, although it appears to spare dietary LA and improve LA incorporation. Other longer chain PUFA cannot substitute for LA. The addition to a diet of a small amount of LA can rapidly normalise the function of the stratum corneum. It is now well recognised that atopic dermatitis is associated with impaired ceramide production within the stratum corneum, which leads to increased water loss, and likely increased allergen absorption.6 The effect of the diet on ceramide production has not been carefully studied in dogs or cats. However, in one study, enrichment of the diet with a mixture of fatty acids (including LA, GLA, EPA and DHA) resulted in an increase in both free, and protein bound ceramides, cholesterol, and free fatty acids in and on the dermis.7 In another study, a commercial dry food based on potato, fish, and animal fat (Eukanuba Response FP), was compared with a home-prepared diet of fish (cod or hake) and potato.8 Disease severity scores improved within 4 weeks of being fed the commercial diet.
Many, perhaps most, studies of the efficacy of PUFA supplementation on CAD are hampered by failure to consider the dietary fat content concurrently ingested by the trial subjects. In one of the few to evaluate supplementation of a controlled diet, an n-3 PUFA supplement enabled a significant reduction in the use of prednisone required to control pruritus after 8 weeks of supplementation.9 Predicting the effect of PUFA within a diet has to take into account the a) total fat content, b) relative proportions of 18-carbon and 20 carbon n-3 and n-6 PUFA, c) absolute amounts of all individual n-3 and n-6 PUFA, d) previous dietary history of the animal, and e) duration of exposure to the diet in question. Describing the fat content of a diet by a simple ratio of n-6 to n-3 PUFA provides very limited and potentially misleading information. In addition, supplementation of a diet with a source of n-3 PUFA (e.g., marine fish oil) will have varying effects depending on the diet and patient. Most commercial diets are highly concentrated in n-6 PUFA, and the addition of a small amount of n-3 PUFA will achieve little. Equally, if the diet is already high in LA, then adding more is very unlikely to have any benefit. Where information on specific dietary fatty acid concentrations is not available, a ratio of total n-6 to n-3 of less than 5 may be effective for reducing pruritus in atopic dermatitis, whereas a ratio less than 3.5:1 may be needed for more, especially for serious inflammatory skin diseases, and ratios as low as 1.3:1 may be optimal. The exact amount of fish oil required to be added depends on the basal diet. Hypersensitivity to dietary antigens is not necessarily a lifelong state. Although not clear, the expert opinion is that in humans, food allergies that start in childhood are often outgrown, whereas food allergy that start in adulthood often persists. The resolution of confirmed food hypersensitivity in dogs and cats has not been well described. In a study of 55 cats with chronic vomiting and/or diarrhoea, 16 cats were diagnosed as having food sensitivity based on elimination-challenge trials.10 However, a further 14 cats responded completely to an elimination diet, but did not recrudesce during a challenge with the staple diet. Whilst some of those cats may not have been challenged with the offending food allergen due to an incomplete dietary history, some cats may have rapidly reestablished oral tolerance. It is possible that following a period of intestinal quiescence, those cats became clinically tolerant to the food protein, despite potentially still having sensitised antigen-specific lymphocytes. A similar study in feline or canine food allergic patients with CFH has not been published.
References
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2. Wiese HF, Yamanaka W, Coon E, et al. Skin lipids of puppies as affected by kind and amount of dietary fat. J Nutr. 1966;89:113–122.
3. Menton DN. The effects of essential fatty acid deficiency on the skin of the mouse. Am J Anat. 1968;122:337–355.
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9. Saevik BK, Bergvall K, Holm BR, et al. A randomized, controlled study to evaluate the steroid sparing effect of essential fatty acid supplementation in the treatment of canine atopic dermatitis. Vet Dermatol. 2004;15:137–145.
10. Guilford WG, Jones BR, Markwell PJ, et al. Food sensitivity in cats with chronic idiopathic gastrointestinal problems. J Vet Int Med. 2001;15:7–13.