Nutritional Therapy in Dermatology

3. Nutritional Therapy in Dermatology

Dull Coat, Xerosis

The coat's sheen is connected to the composition of sebum, a natural wax secreted by the sebaceous glands and stored in the hair follicles. Sebum also has the role of preventing the felting of the hairs by eliminating the relief of the hair scale. Sebum makes the keratin in the hair more elastic and more flexible. The lipids in the composition of the sebum are species and breed specific (Dunstan et al., 2000), but the production and the quality of the sebum is also influenced by the food. Some essential nutrients given in higher quantities than the strict recommended minimal quantities produce a significant improvement in the appearance of the dog's coat. This is notably so with PUFA from vegetable sources (omega 6) and zinc. A combined zinc/linoleic acid supplement improves the coat's brilliance and reduces scale (Marsh et al., 2000).

The sensitivity of PUFA sources to oxidation demands close monitoring of their resistance to oxidation, and increased quantities of vitamin E in the food.

Excessive Shedding

Shedding experienced by dog owners as excessive may be physiological, whether it is continuous or seasonal. The intensity of this shedding depends on many factors including the genetic potential, the hormonal balances, the photoperiod and nutrition.

When excessive shedding leads to a veterinary consultation, an attempt must be made to identify the potential causes of anomalies in the pilary cycle:
- Endocrinopathy
- Unadapted environment
- Relative deficiency of PUFA, biotin, tyrosine, tryptophan, cystine, vitamin E, vitamin A, choline or folic acid.

Many nutrients are used to stimulate hair growth, including biotin (Fromageot & Zaghroun, 1990) and paprika. The addition of paprika (Capsicum tetragonum) to the food increases the intensity of hair coloration and stimulates the hair growth, particularly during shedding (Greer, 1981).

However, no studies have yet proved that shedding in a dog on a balanced diet can be controlled by nutritional or pharmacological measures.

Black Coat with Red Reflex

It is possible to prevent the reddening of the coat of dogs with black coats by enriching the diet with tyrosine. The response time varies according to the hair cycle. If the majority of hairs are in the telogen phase they are replaced more quickly. The hairs that redden during shedding remain red even after supplementation of aromatic amino acids.

Figure 20. Abundant scaling, showing major xerosis in an atopic Labrador. (© P. Prélaud).

Vitiligo

Vitiligo is characterized by depigmented lesions preferentially in the mucocutaneous junctions (Figure 21). Depigmentation is due to the absence of melanocytes. The causes of vitiligo are highly varied and few effective treatments have been identified at this time. In humans, L-phenylalanine is regularly used (Antoniou & Katsambas, 1992; Camacho & Mazuecos, 2002) and has produced good results in dogs (Guaguère, personal communication).

Figure 21. Depigmented vitiligo lesions in a Shar Pei. (© P. Prélaud).

Skin Wound Healing

Nutritionists have studied the nutrients that improve the healing of wounds, so as to be in a position to propose nutritional supplements in the pre- and post-surgery period. Human medicine has a great number of enteral preparations in liquid form. The sought-after properties are stimulation of re-epithelialization and stimulation of the immune system to limit infection. They could potentially be used in adult dogs, but the protein concentration is insufficient for puppies.

Dogs suffering from a protein deficiency (e.g., during a fast due to hospitalization) have delayed wound healing. It is essential to safeguard nitrogen balance to facilitate tissue regeneration, paying particular attention to glutamine and arginine contents in the food. The production of nitric acid from arginine stimulates the expression of the endothelial vascular growth factor.

Zinc deficiency is associated with delayed wound healing. Zinc is essential to cell replication and proliferation.

Iron and vitamin C are involved in hydroxylation of proline, a major amino acid in the structure of collagen. Iron deficiency affects the quality of the scar tissue.

Omega 3 fatty acids have a positive effect on the inflammatory reaction at the site of wound healing. A vitamin E supplement helps protect PUFA's from oxidation.

The positive role of curcumin, aloe vera and bromelaine has been shown in the wound healing process (Fray et al., 2004).

Ideally, these nutrients should be administered 8 weeks before surgery. This period is needed for the PUFA to act effectively in the skin. The treatment must be continued for at least four weeks after surgery, depending on the required length of wound healing.

Atopic Dermatitis

Canine atopic dermatitis, like human atopic dermatitis, is a multifactorial disease in which nutrition can be used at three levels.

- Re-establishment of the Skin Barrier Function

Atopic dogs have problems with function of the skin barrier, especially defects in the intercellular cement formed by the ceramides (Figure 22) (Inman et al., 2001). This allows water loss, increased transcutaneous penetration by antigens and increased adherence of staphylococci to the surface of the corneocytes.

Figure 22. Structure of an intercellular junction. (© Waltham Centre for Pet Nutrition)

- Reduction in Inflammation

By using nutrients acting on the inflammatory (long-chain omega 3 polyunsaturated fatty acids: EPA and DHA) or immune response (probiotics) (Baillon et al., 2004).
- Prevention or Control of Dietary Hypersensitivities

Due to highly digestible and/or hypoallergenic foods.

Reinforcement of the Skin Barrier Function

In vitro studies (keratinocytes cultures) conducted by the Waltham Research Centre have shown that some nutrients (in particular: nicotinamide, pantothenic acid, histidine, inositol and choline) improve the structure and the function of the skin. Others (pyridoxine and proline) stimulate the synthesis of ceramides (Figure 23) (Watson et al., 2003).

In vivo studies have confirmed this approach. After nine weeks of supplementation with a supplement composed of nicotinamide, pantothenic acid, histidine, inositol and choline, the cutaneous water loss was significantly reduced in atopic dogs. The reduction in water loss and so xerosis can have a positive effect of reducing allergen penetration, and also limit bacterial and fungal colonization, which may cause the development of atopic dermatitis.

Figure 23. Measuring the synthesis of skin lipids (From Watson, 2003).

Polyunsaturated Fatty Acids (PUFA)

In the case of pruriginous dermatitis caused by an allergy, omega 3 and omega 6 PUFA may be used to limit skin inflammation, restore the integrity of the hydrolipidic film and limit the transcutaneous penetration of allergens and bacterial and fungal infections. Various studies show that the use of supplements high in PUFA reduces skin inflammation, but does not have any obvious effect on pruritus. They also reduce the dose of long-term corticosteroid therapy when this is necessary (Saevik et al., 2004). The efficacy of such a therapeutic approach in the case of canine atopic dermatitis is more significant in the early stages of the disease (Abba et al., 2005).

In human medicine the preventive use of PUFA is envisaged in the mothers of atopic children. A mother's food is high in omega 3 and omega 6 PUFA and impacts the immune response of breastfed children, favoring a Th1-type response (Das, 2004). Such an approach has not been used in dogs, but it could be tried in dogs of high-risk breeds, like the Shar-Peï and the West Highland White Terrier.

Curcumin

The addition of curcumin can also benefit dogs suffering from atopic dermatitis, through mechanisms that are focused on the immune response (inhibition of mast cell activation, inhibition of lipoxygenase and cyclooxygenase synthesis, immunoglobulins, etc) (Cuendet & Pezzuto, 2000).

The presence of borage oil in food provides interesting results in various allergic manifestations (Quoc & Pascaud, 1996). Borage oil is frequently used in human dietetics and cosmetology and is the only oil that contains more than 20% gamma linolenic acid (GLA).

The efficacy of borage oil is improved when it is used in association with fish oils, which have high EPA and DHA contents (Sture & Lloyd, 1995).

These very long-chain omega 3 fatty acids act in the same way as gamma linolenic acid, albeit through different metabolic processes. They inhibit the synthesis of arachidonic acid and its derivatives, which are responsible for inflammatory manifestations.

Keratoseborrheic States

Primary Keratinization Disorders

Many primary keratinization disorders justify the use of PUFA or retinoids. Retinoids control the proliferation of keratinocytes by reducing the synthesis of sebum and the inflammatory reaction (inhibition of the expression of chemokines). They are much more effective than vitamin A and produce fewer secondary effects. Their use however, is not without risk and they must be part of a prescription in which the owner is informed and monitoring is provided (Table 18).

Vitamin A Responsive Dermatoses

Vitamin A regulates the growth of epidermal cells and the production of sebum. It helps combat seborrhea and the pellicles that often form after a pruritic episode. It acts in synergy with zinc and sulfated amino acids.

Vitamin A responsive dermatosis is a rare and much discussed keratinization disorder described only in the Cocker Spaniel. It is clinically characterized by dull hair and thick, foul-smelling scaling (Figure 24). The diagnosis is based on histopathology that reveals major follicular orthokeratotic hyperkeratosis. Vitamin A supplementation (1000 IU/kg/day) leads to a recovery, although the response is fairly slow. In case of failure or partial remission, retinoids may be used.

Figure 24. Attached scaling lesions in a Cocker Spaniel presenting with vitamin A responsive dermatosis. (© P. Prélaud).

Ichthyoses

Ichthyoses are genetic keratinization problems. Patients present with thick scaling around the pads and over the body from a very early age (Figure 25). Predisposed breeds include Cavalier King Charles Spaniels, Cocker Spaniels, Retrievers, Soft Coated Wheaten Terriers, West Highland White Terriers, Jack Russell Terriers and Rottweilers. Histopathology helps identify the diagnosis. Treatment is based on the combined use of keratolytic shampoos and PUFA or synthesized retinoids (Table 18).

Figure 25. Perinipple ichthyosis lesions in a Cavalier King Charles. (© P. Prélaud).

Idiopathic Seborrheas

The primary seborrheas will appear at a very early age in some predisposed breeds (particularly American Cocker Spaniels). This is a genetic anomaly caused by the accelerated regeneration of the epidermis. The lesions are generalized (oily scaling), sometimes with major localized thickening (on the ventral surface of the neck or in the fold of the elbow, for instance). The diagnosis is based on the elimination of all causes of seborrhea and skin biopsies.

Treatment includes an anti-infection treatment, localized care (clipping and keratolytic shampoos) and synthetic retinoids. They are administered every day for 3 - 5 months. If control is satisfactory, intake is reduced to once every two or three days.

Zinc Responsive Dermatosis

Several zinc salts are available for the treatment of zinc responsive dermatoses (Table 7). The very cheap zinc sulfate can be poorly tolerated (vomiting) and must be administered with meals. Zinc gluconate is generally better tolerated (Guaguère & Bensignor, 2002). Zinc methionine is probably the best absorbed, but it is available only in a preparation in which it is associated with vitamin A and it is expensive. The length of treatment varies from three to eight weeks depending on the animal and must often be life long.

Secondary Seborrheas

Many keratinization disorders may be accompanied by inflammatory dermatoses caused by an allergen or a parasite. They do not justify retinoid treatment. The treatment of the associated infection or the primary cause will control it. Some authors consider that the nutritional requirements are greater during the keratoseborrheic state and that it is accordingly necessary to provide an appropriate diet, enriched with PUFA, vitamin E, zinc and trace elements.

Granulomatous Sebaceous Adenitis

Granulomatous sebaceous adenitis is a genetic disease characterized by destruction of the sebaceous glands, which gradually disappear, causing keratinization disorders in the hair follicle with alopecia and the formation of hair flanges. The lesions appear gradually and can be localized in any region of the body (Figures 26a & 26b).

Figure 26a. Granulomatous sebaceous adenitis in an Akita Inu: irregular alopecia over the whole trunk, associated with a keratoborrheic state. (© P. Prélaud).

Figure 26b. Same dog as in Figure 26a, after two months’ treatment with polyunsaturated fatty acids and keratin modulating shampoo. (© P. Prélaud).

All breeds can contract this disease, but there are some clear breed predispositions: Akita Inus, Poodles, Samoyeds and Lhassa Apsos. The diagnosis is based on the examination of multiple biopsies that confirm the destruction of the sebaceous glands. The treatment requires localized care (keratin modulation shampooing) and general treatments: essential fatty acids, corticotherapy, cyclosporine, synthetic retinoids (Table 19). The prognosis is always guarded. Given the potential secondary effects (retinoids, corticoids) or the cost (cyclosporin A) of alternative therapeutics, the administration of PUFA must be attempted first, in association with keratin modulating shampoo.

Various Immune Dermatoses

Vitamin E, due to its antioxidant action, and PUFA are commonly used on their own or as an adjuvant for immune mediated dermatoses.

Vitamin E (400 - 800 IU BID) is used as an adjuvant for lupus (Scott et al., 2001) and dermatomyositis (Hargis & Mundell, 1992). Used on its own, it is only effective in a very limited number of cases.

PUFA are used for their anti-inflammatory or immunomodulating action in the treatment of lupoid onychodystrophies with excellent results in one in three cases (Mueller et al., 2003).

Recurring Bacterial Infections

Nutrition can play an essential role in controlling recurring infections by helping to reestablish the skin barrier (skin barrier-type nutrients, PUFA) or by helping to control allergic inflammation (PUFA, hypoallergenic foods).

Prophylactic Nutrition

In canine dermatology, nutritional interventions continue to be almost exclusively devoted to therapeutic functions. In human dermatology however, especially allergic dermatology, nutrition is used preventively (Table 19).

Such an approach could be interesting, the more difficult problem is the identification of individuals at risk. This is problematical in humans (Osborn & Sinn, 2003), but is much easier in dogs, as certain breeds and lines are predisposed to nutritional or immune dermatoses (Scott et al., 2001).

Hypoallergenic and Highly Digestible Foods

Hypoallergenic and highly digestible foods are used in dermatology for therapeutic purposes. In human medicine these foods are mainly used in the prevention of food allergies in high-risk children, or even breastfeeding mothers. Hydrolysates are used for high-risk children that cannot be breastfed to significantly reduce the risk that clinical manifestations of atopy will develop (Osborn & Sinn, 2003). Such an approach could be useful in canine medicine, but it must undergo controlled clinical studies.

Probiotics

In humans, there is a correlation between the use of antibiotics in infancy or in the mother during the perinatal period and the development of atopic dermatitis. Conversely, random double-blind studies show that the administration of probiotics to mothers at risk limits the occurrence of manifestations of atopic dermatitis (extrinsic form) in children (Flohr et al., 2005).

In dogs, the addition of probiotics in the food presents technical problems (Weese & Arroyo,2003). It is however possible to include them in a dry food and to observe their effect on immune response (Baillon et al., 2004). If the goals of feeding such a food are aimed at the gastrointestinal tract, preventive or curative use in atopic dogs could also be practical.

In high-risk breeds, with respect to dermatology it would be useful to try to prevent hypersensitivity phenomena by modifying the mother's food during gestation, as occurs in human medicine. (© Lenfant)

Polyunsaturated Fatty Acids

Recurring bacterial infections are most often caused by allergic dermatopathies (dietary hypersensitivity, atopic dermatitis) or non-specific skin defense problems. In both cases PUFA supplementation or a skin barrier cocktail may limit the risks of a relapse. It is essential however that the causes of recurring pyodermititis be identified before diagnosing an idiopathic recurring pyodermititis (Table 12).

PUFA supplementation in human mothers during pregnancy and lactation helps limit the dietary hypersensitivity phenomena in children (Korotkova et al., 2004). Such an approach could be useful in bitches of high-risks breeds like Shar-Peis or West Highland White Terriers.

Conclusion

Food plays a fundamental role in cutaneous homeostasis and in the treatment of many inflammatory dermatoses. The study of the diet is therefore an integral part of the dermatological history. The correction of dietary imbalances (with respect to zinc and essential fatty acidsin particular) is a necessary factor in good dermatological therapy.

It is important to challenge ideas that impede the management of chronic pruriginous dermatitis on a daily basis. These include the harmfulness of food based on their origin, the value of IgE doses of dietary allergens, the absence of flea infestation opportunities and the harmfulness of short-term corticosteroid therapy.

The treatment of keratinization disorders or allergenic dermatites involves the use of nutrients that reinforce the skin barrier function, or even play an anti-inflammatory role. The future is open to the possible use of food for prophylactic purposes (probiotics, essential fatty acids, etc) in animals at risks of skin disease.