Nutritional Dermatosis

2. Nutritional Dermatosis

Nutritional dermatoses may affect cats in many different ways which are listed in Table 2.

Specific Nutritional Imbalances

Protein Deficiency

Hair consists of 95 % protein, and is rich in sulphur amino acids such as methionine and cystine. The growth of hair and renewal of the skin will absorb 30 % of dietary protein (Scott et al., 2001). Any situation where protein requirements are not fulfilled will lead to poor coat and skin with generalized scaling, loss of pigment, poor hair growth, easy shedding, thin, dull and brittle hair.

Protein deficiency can either be due to a lack of supply i.e., poor quality diet, unbalanced home prepared food, low protein diet or to protein loss related to a systemic illness such as protein losing gastro-enteropathy, nephropathy, hepatopathy, or chronic bleeding. The reason for the nutritional imbalance needs to be identified and corrected.

Essential Fatty Acid Deficiencies

Essential fatty acids are not synthesized by the organism, thus their supplementation in the diet is "essential". They are primarily the precursors of two families of polyunsaturated fatty acids (PUFA), omega-6 fatty acids and omega-3 fatty acids.

PUFA fulfill five main functions:

• Incorporation in the structure of the cell membrane, which gives it its flexibility and permeability
• Production of eicosanoids (leukotrienes, prostaglandins, etc.)
• Maintenance of the skin barrier permeability (especially omega-6 fatty acids)
• Cholesterol metabolism and transport
• Immunomodulation through an influence on antigen presenting cells and T lymphocytes

PUFA deficiencies are observed in animals suffering from malassimilation or animals fed with poor-quality diets or diets that have been overheated for a lengthy period. The cutaneous signs are xerosis, dull hair and a keratoseborrheic disorder. The response to PUFA supplementation is rapid.

- Linoleic acid, a precursor of omega-6 fatty acids, is abundant in most vegetable oils. It represents more than 70% of the fatty acids in evening primrose oil and more than 50% in sunflower oil, corn and soy oils.

Cats are deficient in Δ-6 desaturase which is the enzyme needed for the first step of the transformation of linoleic acid into arachidonic acid. Thus linoleic acid and arachidonic acid are both essential nutrients for the cat (Figure 3).

- Alpha linolenic acid, a member of the omega-3 fatty acids, is found in green vegetables, fruits, grasses and plankton, and in concentrated form in the oil of plants like soy, flax, or linseed. The oils of fish from cold waters contain very high levels of two long-chain fatty acids derived from alpha linolenic acid: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Figure 3). These two fatty acids participate in the fluidity of the cell membranes.

Figure 3. Hepatic synthesis of long-chain omega-6 and omega-3 fatty acids from their respective precursors.

In addition to their anti-inflammatory, anti-neoplastic, immuno-stimulant, and cardio-protective properties, omega-3 fatty acids are also often used as anti-pruritic agents. Even in situations of an open wound or post-surgery, the benefit of supplementation still outclasses the mild reduction of perfusion which could potentially impede the healing process (Scardino et al., 1999).

Zinc Deficiency

Zinc is a key element in many cellular mechanisms. Considering the fast turn over of epidermal cells, zinc is particularly necessary for a healthy skin and coat. Zinc is also needed for the biosynthesis of fatty acids, for the metabolism of vitamin A and for the inflammatory and immune response. Absolute dietary deficiency has not been reported in the cat but absorption of zinc can be inhibited by excessive levels of calcium, iron or copper due to competition for the absorption channels. Phytate present in cereals chelates zinc and will reduce its dietary availability. Other conditions preventing the absorption of zinc such as enteritis can also lead to depletion of the metal but usually the symptoms of the protein deficiency will be clinically apparent before signs of zinc deficiency occur.

Vitamin E Deficiency

Pansteatitis (synonyms: feline vitamin E deficiency, vitamin E deficiency steatitis or yellow fat disease) is characterized by diffuse nodules of fat or fibrous tissue, especially in the groin or on the ventral abdomen. The cat is depressed, febrile, and reluctant to move or jump. Palpation is painful due to inflammation of the subcutaneous fat. Nutritional pansteatitis has been reported in young and obese cats fed a diet containing large amounts of unsaturated fatty acids and/or insufficient vitamin E. Canned red tuna, sardines, herring and cod but also diets based on pig brain have been incriminated. Inactivation of vitamin E can occur during food processing or by fat oxidation. A case of pansteatitis associated with a pancreatic tumor has been described (Fabbrini et al., 2005).

Histologically, the subcutaneous fat will exhibit ceroid deposits which are pathognomonic of the condition. In lesions without ceroid, specific staining will have to be performed to differentiate pansteatitis from pancreatic or traumatic panniculitis (Gross et al., 2005).

Vitamin A Deficiency

Cats are unable to convert β-carotene from plants to vitamin A and thus need to receive preformed vitamin A. Among several functions, vitamin A is required for ocular function but also for skin turn over. With vitamin A deficiency, the cat will exhibit a poor coat, alopecia and generalized scaling. The supply of a balanced, meat containing diet is usually sufficient to cure the condition. Vitamin A supplements are not recommended in the cat when fed a complete food because of the risk of hypervitaminosis A.

Hypervitaminosis A

This condition was rather common in the past when cats were fed raw liver. It is still seen occasionally when the owner gives large amounts of cod liver oil supplement. The signs are mainly osteo-articular due to the cat’s inability to move. As a consequence, the cat will be unable to groom properly, resulting in an unkempt, matted coat.

Vitamin B Deficiency

B complex vitamins are treated as a group. They are water soluble vitamins that cannot be stored. Biotin, riboflavin, niacin, inositol, pantothenic acid and pyridoxine are important for the quality of the skin barrier and deficiencies will lead to dry flaky seborrhoea accompanied by alopecia, anorexia, weight loss and pruritus.

Biotin deficiency sometimes occurs with consumption of numerous uncooked eggs. The avidin in the egg white binds to biotin and blocks its absorption. This will lead to a papulocrustous dermatitis.

A deficiency in riboflavin will lead to head and neck alopecia in cats. Niacin deficiency has also been described in cats fed a low protein high corn diet. Niacin and pyridoxine deficiencies can be produced experimentally. However, appropriately formulated commercial pet food contains high quantities of these vitamins.

Supplementation of B vitamins might be necessary with anorexia or polyuria. Vitamin B complex can be found in brewer’s yeast and in balanced commercial food. Certain B vitamins work in synergy with histidine to improve the barrier function of the epidermis and decrease the TEWL (transepidermal water loss) (Watson et al., 2006).

Cats have high requirements in terms of water-soluble B vitamins and they are unable to convert β-carotene into retinol (active form of vitamin A). These characteristics show that cats are adapted to a carnivorous diet: under natural conditions, they do not lack these vitamins since they are present in large quantities in animal tissues. (®Renner/RC).

Dietary Hypersensitivities

The term dietary hypersensitivity or food allergy is used by many veterinarians and owners as a broad term to describe any immunological and non-immunological reactions to ingredients of the diet that result in a clinical adverse reaction in an otherwise healthy cat. This adverse reaction may occur in the form of gastrointestinal problems and/or cutaneous abnormalities typically associated with self trauma due to pruritus (Table 3).

In the cat, adverse food reactions are considered to be relatively more common than in the dog (Scott et al., 2001). In one search of feline records in a number of veterinary colleges, feline adverse food reaction occurred in 10% of the patients presented with allergic skin disease (Chalmers & Medleau, 1989). It was the second most common disorder after flea bite hypersensitivity. However, another more recent report suggested atopic dermatitis to be much more common than adverse food reaction (73 versus 23% of 90 cats) (Prost, 1998). This may reflect the different location, different setting of private dermatology referral practice versus veterinary teaching hospitals, the increased awareness of other hypersensitivities besides flea hypersensitivity in the cat, and/or owners increasingly willing to pursue involved diagnostic procedures for their pets. The prevalence of food hypersensitivity in humans is reported to be approximately 10% in infants (Bock, 1987) and 2% in adults (Young et al., 1994). No such data is available for cats to the authors’ knowledge.

Etiology

In humans, non-immunological food reactions like toxic food reactions (e.g., toxins secreted by Salmonella spp.), pharmacologic reactions (e.g., caffeine) and metabolic reactions (e.g., lactase deficiency) comprise the majority of food-related problems (Sampson, 2003). The term hypersensitivity is used more stringently only for immunologically mediated reactions to food ingredients. Type I hypersensitivities are most common, although type IV mediated food hypersensitivities and mixed forms have been described (Figure 4).

Figure 4. Pathogenesis of adverse food reaction.  

In cats, type I hypersensitivity has been presumed as edema is the predominant clinical sign in some cats (Walton, 1967). However, in most clinical cases, the pathophysiological mechanism is not determined and adverse food reaction is diagnosed exclusively by the association between diet and clinical signs.

Break in Immune Tolerance

In healthy humans, intact food antigens penetrate the gastrointestinal tract and enter the circulation without any clinical signs because most individuals develop tolerance to ingested antigens. This tolerance may be based on the induction of regulatory T cells (Smith et al., 2000; Zivny et al., 2001) or T cell anergy (where T cells are stimulated by antigen presenting cells via MHC class II molecules but without appropriate costimulatory signals) (Chehade & Mayer, 2005). Maintenance of this immune tolerance depends on a variety of factors listed in Table 4.

In humans with a genetic predisposition for atopy, class switching of B cells leads to the production of antigen-specific IgE. A breakdown in oral tolerance and development of hypersensitivity may occur when food allergens penetrate the mucosal barrier and reach IgE antibodies bound to mast cells. Degranulation of these mast cells leads to mediator release, inflammatory cell influx and subsequent clinical signs. In the cat, little is known about the mechanisms underlying oral tolerance and hypersensitivity.

Dietary Allergens

In three studies the most common allergens involved based on provocative challenge were fish, beef and dairy products (Guaguere, 1993; Walton, 1967; White & Sequoia, 1989). One third of the cats could not tolerate any commercially prepared diet without recurrence of clinical signs. A list of reported offending allergens is given in Table 5.

In one study, almost 30% of 55 cats with chronic gastrointestinal problems showed food hypersensitivity (Guilford et al., 2001). Half of these cats reacted to more than one protein. The clinical feature identified to be most sensitive for the diagnosis of adverse food reaction was the concurrent occurrence of gastrointestinal and cutaneous signs.

In humans and dogs, the major food allergens identified so far have been water soluble glycoproteins with molecular weights ranging from 10 - 70 kD (Martin et al., 2004; Sampson, 2003). No such data is available for the feline to the authors’ knowledge.

Predisposing Factors

Many factors may be involved in the development of feline food hypersensitivity.

Genetic Predisposition - In two studies, Siamese or Siamese cross breeds accounted for approximately 30% of the cases and a genetic predisposition for those cats was proposed (Carlotti et al., 1990; Rosser, 1993). The relative risk factor of Siamese for food hypersensitivity in one study was 5.0 (Rosser, 1993). In the other report, 3 of 10 cats with adverse food reactions were Siamese cats (Carlotti et al., 1990).

Maldigestion - Dietary proteins are typically broken down by gastric and intestinal enzymes into amino acids and small peptides which are assimilated by the intestinal mucosa. If digestion is defective, the molecular weight of the proteins is much higher and the risk for break down of tolerance increased.

This explains why chronic intestinal inflammatory disease may be conducive to the development of dietary hypersensitivity. However, if the gastrointestinal inflammation seen in cats with chronic bowel problems was originally due to other causes and led to food hypersensitivity or if this hypersensitivity is solely responsible for the inflammatory changes is not known at this point.

Other Hypersensitivities - Concurrent hypersensitivities such as flea bite hypersensitivity or atopic dermatitis are known in dogs with dietary intolerance and may also be a complicating factor in cats. In one of the first reports studying feline food hypersensitivity, 3 of 14 cats had concurrent hypersensitivities (White & Sequoia, 1989). In a recent article, 6 of 16 cats with allergies were diagnosed with a combination of adverse food reaction and atopic dermatitis (Waisglass et al., 2006). Another report described 90 allergic cats, 16 cats had an exclusive adverse food reaction, 4 cats had concurrent atopic dermatitis and adverse food reaction and one cat was additionally allergic to fleas (Prost, 1998). Thus almost a quarter of cats with an adverse food reaction had concurrent hypersensitivities.

The Siamese appears to have an increased tendency for food hypersensitivity. (©Yves Lanceau/RC).

Clinical Features

In the cat, clinical signs of adverse food reactions vary from pruritus with associated self trauma, eosinophilic granuloma, respiratory signs to gastrointestinal problems.

Head and Neck Pruritus -  Head and neck pruritus was reported in cats with dietary hypersensitivity (Guaguere, 1993; Medleau et al., 1986; Stogdale et al., 1982). Alopecia, crusting, erosions and ulcerations are seen in the affected area as a consequence of self trauma (Figure 5). Pruritus is often severe and may be non-responsive to medical therapy. Secondary infections with bacteria or yeast are not uncommon. Pruritus and thus lesions can spread to other body sites and become generalized with time.

Figure 5. Consequences of pruritus in a domestic short hair cat. Face, head, pinnae and neck can all be affected in various combinations. (©R. Mueller).

Miliary Dermatitis -  Small papules and crusts either localized (frequently on the head and neck) (Figure 6) or generalized are also seen with dietary hypersensitivities (Mueller, 2000, Scott et al., 2001). In one study, 21% of the cats with adverse food reaction showed this reaction pattern (White & Sequoia 1989). In another study, almost half of the cats with adverse food reactions had military dermatitis (Carlotti et al., 1990).

Figure 6. Characteristic lesion of miliary dermatitis in a domestic short hair cat. Small papules and crusts on the trunk characteristic of military dermatitis. (©R. Mueller).

Non-inflammatory Alopecia -  Self-induced, bilaterally symmetrical alopecia with no macroscopic lesions is also a common reaction pattern associated with feline adverse food reaction (Mueller, 2000; Scott et al., 2001). Most commonly affected sites are the ventrum, inguinal area, thighs and flanks (Figure 7) Owners may or may not observe excessive grooming as a cause of the alopecia, as some cats do not exhibit that behavior in the presence of humans ("closet groomers"). In one report, 10% of all cats with adverse food reaction showed exclusively alopecia. In another report of 21 cats with presumptive psychogenic alopecia, adverse food reaction was diagnosed in more than half of the cats (Waisglass et al., 2006).

Figure 7. Consequences of an allergic pruritus in a domestic short hair cat. Noninflammatory alopecia on the flanks and lateral thighs. (©R. Mueller).

Eosinophilic Granuloma -  Eosinophilic plaques are the most frequently reported lesion of the eosinophilic granuloma complex in cats with adverse food reactions, but other lesions such as linear granuloma have been reported (Carlotti et al., 1990; White & Sequoia, 1989). Eosinophilic plaques are well circumscribed, erythematous, severely pruritic and often ulcerated plaques typically on the abdomen or medial thighs (Figure 8). Linear granulomas are non pruritic, raised, firm, yellowish plaques, most commonly on the caudal thighs (Figure 9).

Figure 8. Facial eosinophilic plaque in a domestic short hair cat. (©R. Mueller).

Figure 9. Linear granuloma on the caudal thigh of a domestic short hair cat. (©R. Mueller).  

Gastrointestinal Problems -  Vomiting, diarrhea and/or flatulence may be clinical signs of feline adverse food reaction (Guilford et al., 2001; Stogdale et al., 1982). Vomition may occur within minutes after eating or hours after the meal and often occurs infrequently. In many cats, diarrhea is due to large bowel dysfunction and thus excessive straining to defecate, mucus and/or blood in the feces may be seen. In one study of 55 cats with chronic gastrointestinal problems, almost one third were diagnosed as food sensitive based on resolution of clinical signs with an elimination diet and recurrence of those signs, when challenged with the previous diet. Most of these cats had a history of vomiting (56%) and a quarter of the cats exhibited chronic diarrhea. The remaining 3 cats had both clinical signs (Guilford et al., 2001).

Diagnosis

Cutaneous signs of feline adverse food reactions usually present themselves as reaction patterns with a number of possible underlying causes, thus a thorough diagnostic work-up is essential in these patients. The list of differential diagnoses depends on the presenting cutaneous reaction pattern and is shown in Table 6. Diagnostic tests or trial therapies to rule out differential diagnoses depend on the presenting signs and may include evaluation of cutaneous cytology, superficial and deep skin scrapings, fungal cultures, ectoparasite treatment trials and skin biopsies.

Intradermal Testing/serum Testing for Food Allergen-specific Ige -  It is tempting to measure dietary allergen-specific IgE to identify the offending dietary allergen(s) and to use the results to choose a new diet. Although sometimes recommended by individuals and laboratories offering these tests, at this time there is no evidence available to the authors to justify such tests. In the dog, published data show that these tests are unreliable (Jackson & Hammerberg, 2002; Jeffers et al, 1991; Kunkle & Horner, 1992; Mueller & Tsohalis, 1998; Wilhelm & Favrot, 2005). In the cat, only one report evaluated serum antigen-specific IgE in cats with adverse food reactions (Guilford et al., 2001). Only half of the cats with confirmed adverse food reaction had a positive test result. The majority of cats either tolerated the food antigen that they had tested positive for or they had never been exposed to it and thus hypersensitivity seemed unlikely. Only 25% of the cats showed results that were consistent with the results of their elimination diet and re-exposures.

Home-prepared Elimination Diets -  The only reliable means to diagnose adverse food reaction in the cat is currently a commercial or a home-prepared elimination diet with a protein source the cat has not been exposed to (Mueller, 2000; Scott et al., 2001). Examples of possible protein sources are given in Table 7. Such a diet is typically not nutritionally balanced, but may be fed in adult animals for short periods of time (for the trial period, up to 12 weeks) without clinically apparent adverse effects. The protein source should be boiled, grilled or prepared in a microwave. The method of preparation depends on the individual circumstances, owner and cat. Some cats will accept a mixture of a protein and a carbohydrate source, in these cases a combination of both may be fed. However, most cats will prefer a diet based on protein sources only. Although taurine levels in meat are sufficient for cats (Wills, 1991), particularly young animals on a home-prepared elimination diet may benefit from vitamin and mineral supplementation without flavors or additives (Scott et al., 2001; Wills, 1991).

Commercial Elimination Diets -  As alternative protein sources are sometimes difficult to obtain and require preparation, some owners may only be willing to use a commercial diet. Although numerous hypoallergenic diets are on the market, it is important to remember that the frequency of an adverse reaction to a protein is first and foremost related to the frequency this particular protein is fed to our feline companions. Lamb, fish and chicken, in the past considered first choices for elimination diets, are sometimes reported to be implicated in adverse food reactions of individual cats. These ingredients can still be effective in individual patients but only food with proteins that exclusively come from selected sources that the patient was not exposed to previously are acceptable.

Alternatively, hydrolysed diets may be fed. These foods are formulated on the basis of protein hydrolysates. The purpose of the hydrolysation is to fractionate the proteins into small peptides of low molecular weight (Figure 10).

Figure 10. Lower allergenicity of hydrolysed proteins versus intact proteins. Degranulation of mast cells (which leads to the release of histamine, responsible for inflammation), results from the binding of two amino acid sequences or epitopes on two immunoglobulins located on the mast cell surface. The lower the molecular weight of the protein, the lower the likelihood of containing these two amino-acid sequences.

These peptides are less antigenic and more digestible and thus offer less stimulation to the gastrointestinal immune system. Thus, hydrolysed diets are theoretically the most suitable commercial elimination diets. In the dog, studies have documented clinical improvement of allergic patients on hydrolysed diets (Biourge et al., 2004; Loeffler et al., 2004; Loeffler et al., 2006). No such studies have been conducted in cats to the authors’ knowledge.

Concomitant Treatments -  Antipruritic and/or antimicrobial treatment may be indicated during the elimination diet. The cat may also have concurrent disease that requires continuous administration of drugs. In these cases, the prescription of flavored medication must be avoided, as small amounts of offending allergens may lead to clinical signs and prevent remission with the diet. If medication is usually administered with food, any potential protein source previously fed must be avoided.

If there are several cats in the household, either the hypersensitive cat must be prevented from access to the other cats’ food, or all the cats must be given the same elimination diet. (©Yves Lanceau/RC).

Special Circumstances

Multi-pet households  -  If more than one animal lives in the same household, then the other animals must be fed separately. This is only possible, if the animals are housed completely separately or if the other animals feed rapidly and thus will empty their food bowl in a very short time when placed into a room without the patient with suspected adverse food reaction. Otherwise it is prudent to feed all the animals in the household the same elimination diet to avoid accidents, where the patient consumes additional food from other pets that will most likely prevent clinical improvement.

Outdoor Cats  -  Many cats either live predominantly outdoors or at least have free and unlimited access to the outside. They may wander into other back yards or houses and help themselves to pet food available there. Thus, ideally these patients need to be kept indoors for the duration of the diet, which can be difficult for the cat and owner.

Cats that typically hunt mice or birds will continue that habit during the dietary trial. Ideally these patients should be kept indoors for the duration of the elimination and challenge dietary trials. (©Yves Lanceau/RC - Bengale).

Fussy Eaters -  Some cats may not like the new food offered to them during the diet trial. Cats can be determined and few owners will tolerate refusal of any given diet for more than a couple of days. With a home-prepared diet, warming up the food, salting it very slightly or preparing it differently may entice the cat to accept it. With commercial diets, a gradual change from the original food to the diet over three or four days may increase the chance of acceptance. If neither of these measures is helpful, a new elimination diet may need to be formulated.

Monitoring the Diet -  Compliance with the diet can be difficult not only considering the patient, but also the owner. A thorough client education supported by written instructions will increase the chances of success. Every family member and visiting friends must be informed of the need for strict adherence to the agreed diet trial.

A telephone call a few days after instituting the diet will be helpful in identifying possible problems. At that time, any questions the owners may have are answered. Regular appointments after three to four and six to eight weeks are needed to monitor compliance, motivate and emotionally support the owner. Depending on the food and the cat, weight gain or weight loss may ensue. The owner must be instructed to monitor the cat’s weight and if there is weight gain, diet intake should be decreased. If the patient loses weight, more food should be offered.

Length of the Diet and Interpretation of Results -  A diet trial should be conducted for six to eight weeks. If remission is achieved faster, then of course the diet can be discontinued earlier. After the diet trial, the previous food is fed again and should lead to a recurrence of clinical signs within hours to at the most, two weeks. At this point reinstitution of the elimination diet with subsequent resolution of clinical signs confirms the diagnosis of adverse food reaction. If however after two weeks no deterioration has occurred, then improvement was due to other factors such as treating secondary infections, change of seasons or concurrent ectoparasite treatment trial.

If there is spectacular improvement and complete remission occurs, judgement of success is simple. However, if there is partial improvement, interpretation is more difficult. Scoring systems for pruritus (Table 8) and/or lesions or digital photographs may be helpful in these patients. A provocative test is as important in these patients as in the cats with complete remission on the diet to ascertain the diagnosis.

Sequential rechallenge with the introduction of one protein source every one or two weeks allows correct identification of the offending allergen(s). Although many owners are reluctant to perform such a sequential rechallenge due to the associated emotional and organizational efforts, knowledge of the type of allergens involved frequently permits a wider choice of diets likely to be tolerated long term. Alternatively, the elimination diet may be continued long term. With a home-prepared diet, a nutritionist should be consulted to balance the diet and avoid nutritional deficiencies.