Nutrition and Dermatology
Introduction
The skin is the largest organ in the body and has essential protective and homeostatic functions. In small breeds, 25–30% of an animal's daily protein intake may be required for maintenance of healthy hair and skin.
True nutrient deficiencies in companion animals are rarely seen when good-quality commercial diets are available. However, nutrient-responsive dermatoses are recognised and adverse reactions to foods can result in skin disease.
This lecture will examine nutritional factors that affect the skin and hair and have a role in the treatment of some skin diseases.
Protein and Fats
Protein and fats (important source of energy) are required for the growth of hair and keratinocyte proliferation and differentiation. Diets deficient in protein and fats result in poor skin health.
Essential Fatty Acids (EFAs)
Cis-linoleic acid (LA 18:2n-6) and alpha-linolenic acid (ALA 18:3n-3) are polyunsaturated essential fatty acids (EFA) that cannot be synthesised in the body and must be supplied by the diet. In the cat, arachidonic acid is also an EFA.
Ingested ALA and LA are metabolised by animal cells that contain elongases and desaturases to form other important compounds (Figure 1) (VIN editor: Figure 1 was not provided at the time of publication). The skin lacks delta 5 and delta 6 desaturase enzymes and steps involving these enzymes take place in the liver and metabolites are transported to the skin.
In the skin, EFAs are found mainly in phospholipids, which are a major component of lipid bilayers of cell membranes. Essential fatty acids are also an important component of ceramides which along with free fatty acids and cholesterol, make up the intercellular lipids of the stratum corneum and are important for barrier function.
During inflammation, arachidonic acid (AA) is liberated from cell membranes by the action of phospholipases and is metabolised by lipoxygenase and cyclooxygenase enzymes to form proinflammatory eicosanoids (prostaglandins, thromboxanes, and leukotrienes). Dihomo-gamma-linolenic (DGLA) and eicosapentanoic (EPA) acids compete for the same enzyme systems but their metabolites have anti-inflammatory effects.
Clinical Applications of EFAs
Essential fatty acids have the potential to affect allergic and other forms of skin inflammation. Possible modes of action include:
Dihomo-gamma-linolenic acid, EPA and DHA compete with AA for the lipoxygenase and cyclo-oxygenase enzymes resulting in production of anti-inflammatory eicosanoids.
Metabolism of EPA and DHA may lead to the production of resolvins with anti-inflammatory and immunoregulatory properties.1
Essential fatty acids incorporated into cell membranes may benefit the epidermal lipid barrier.
Modulation of cytokine production, inhibition of cellular activation and cytokine secretion.2
Essential fatty acids have been used as therapeutic agents in canine atopic dermatitis (CAD), feline allergic dermatitis, keratinisation defects, lupoid onychia, lupus erythematosus, hepatocutaneous syndrome, and zinc-responsive dermatosis.
Due to lack of randomized controlled trials, it has recently been concluded that it is unclear whether EFA supplements are of benefit for management of CAD.3 However, EFAs were shown to have a steroid-sparing effect in CAD4 and controlled studies have demonstrated a benefit of EFA-rich diets5,6.
Formulation and Administration
Evening primrose, borage or blackcurrant oils are good sources of gamma-linolenic acid (GLA). Flax, flax oil, linseed oil, and marine fish oil are good sources of omega-3 FAs.
50–300 mg/kg/day of omega-3 FAs is recommended for management of inflammatory skin disease in pets.7 Good-quality diets often contain much higher levels of FAs than available supplements.7 Owners should be advised to continue EFA supplementation for 9–12 weeks before assessing efficacy.
Adverse Effects of EFA Supplementation
Soft stools, flatulence, fishy breath. Weight gain and pancreatitis are possible concerns.
Vitamin A and Retinoids
Retinoids include naturally occurring and synthetic vitamin A derivatives. They are essential regulators of growth and differentiation of epithelial tissues and act by binding to nuclear receptors and activating genes in a manner similar to steroids and thyroxine.8 Vitamin A, isotretinoin and acitretin are administered orally. Tretinoin is available as a topical formulation.
Therapeutic Indications
Retinoids have been used for the treatment of primary keratinisation defects including primary idiopathic seborrhea, sebaceous adenitis, Schnauzer comedo syndrome, ichthyosis, actinic keratosis, and feline acne (topical tretinoin - used sparingly).
Vitamin A is typically administered at a dosage of 1000 IU/ kg orally q 24 h. Responses are usually seen in four to six weeks. Vitamin A can cause keratoconjunctivitis sicca and tear production should be monitored. Retinoids have the potential to be teratogenic.
Vitamin E
Vitamin E deficiency can result in anorexia, pyrexia, and subcutaneous nodules in cats fed diets rich in highly unsaturated fatty acids with inadequate vitamin E (red meat tuna). Vitamin E protects against free radicals and peroxide damage and has been used in the management of a number of immune-mediated and autoimmune dermatoses.7
Zinc
Zinc is a cofactor for many metalloenzymes and important in many biological functions including regulation of the immune response, modulation of keratogenesis, and wound healing. Zinc deficiency can lead to alopecia, ulceration, dermatitis, and secondary infections. There is a close association between zinc and EFA metabolism.7
Zinc-responsive dermatosis is recognised in dogs and two syndromes are described:
Syndrome 1
Siberian huskies, Malamutes and other Nordic breeds fed well-balanced diets. Genodermatosis related to decreased intestinal absorption of zinc.
Syndrome 2
Young growing dogs fed poor-quality diets low in total fat and EFAs, or cereal diets containing high levels of phytates that bind zinc. Uncommon nowadays with improved quality of diet.
Clinical Signs
Erythema, scaling, and crusting over the periorbital skin, nasal planum, elbows, hocks, and footpads. Onychomalacia may be observed. Secondary yeast and bacterial infections are common.
Signalment, history, and clinical signs suggest the diagnosis which is confirmed on histopathological examination showing superficial perivascular dermatitis with marked, confluent parakeratotic hyperkeratosis. Measurement of serum zinc concentration is unreliable.
Treatment
Syndrome 1 cases require lifelong zinc supplementation and a good-quality, EFA-rich diet.
Syndrome 2 cases respond to dietary improvement and short-term zinc supplementation.
Lethal Acrodermatitis of Bull Terriers
Genodermatosis affecting young animals characterised by acral skin eruptions, nail dystrophies, behavioural disturbances, and immunosuppression. Possibly associated with disturbances of zinc and copper metabolism. There is no effective treatment and no response to zinc supplementation.
Superficial Necrolytic Dermatitis
(Syn: metabolic epidermal necrosis, hepatocutaneous syndrome necrolytic migratory erythema).
Disease is usually associated with either hepatic disease or glucagonoma.8 Metabolic changes include hypoaminoacidaemia, carbohydrate intolerance, and concurrent diabetes mellitus. Keratinocyte damage due to cellular starvation and altered zinc and EFA metabolism may contribute to skin lesions.
Clinical Signs
Middle-aged to older dogs and rarely cats.
Erythema, scaling and crusting over the muzzle, periocular skin, pinnae, elbows, hocks, ventrum, scrotum, and feet. Fissuring of footpads with exudation. Systemic signs include lethargy, anorexia, weight loss, polyuria, and polydipsia. Skin lesions may precede systemic disease.
Diagnosis
History, clinical signs, histopathological examination, and demonstration of liver or pancreatic disease by blood tests and diagnostic imaging. Ultrasonography may show a characteristic "honeycomb" liver. Histopathology shows parakeratotic hyperkeratosis; upper epidermal pallor and hyperplasia of basal and suprabasal keratinocytes. Most cases die or are euthanased within five months.
A good-quality diet, zinc and EFA supplementation, and high-quality protein (3–6 egg yolks per day) may be beneficial. Intravenous amino acid infusions can result in variable periods of remission. Surgery is indicated for a pancreatic tumour, although hepatic metastases occur.
Copper
Copper deficiency may be seen in kittens and puppies associated with a dietary deficiency or excess of competing minerals.
Causes loss of hair pigment and a poor hair coat.
References
1. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med. 2002;196(8):1025–1037.
2. Olivry T, Marsella R, Hillier A. The ACVD task force on canine atopic dermatitis (XXIII): are essential fatty acids effective? Vet Immunol Immunopathol. 2001;81(3–4):347–362.
3. Olivry T, Foster AP, Mueller RS, McEwan NA, Chesney C, Williams HC. Interventions for atopic dermatitis in dogs: a systematic review of randomized controlled trials. Vet Dermatol. 2010;21(1):4–22.
4. Saevik BK, Bergvall K, Holm BR, Saijonmaa-Koulumies LE, Hedhammar A, Larsen S, Kristensen F. 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(3):137–145.
5. Bensignor E, Morgan DM, Nuttall T. Efficacy of an essential fatty acid-enriched diet in managing canine atopic dermatitis: a randomized, single-blinded, cross-over study. Vet Dermatol. 2008;19(3):156–162.
6. Taugbøl BB, Vroom MW, Nordberg L, Leistra WHG, Sinke JD, Hovenier R, Beynen AC, Pastoor FJH. A randomized, double-blinded, placebo- controlled multicenter study on the efficacy of a diet with high levels of eicosapentaenoic acid and gamma-linolenic acid in the control of canine atopic dermatitis. Vet Dermatol. 2004;15(S1):11–12.
7. Roudebush P, Schoenherr WD. Skin and hair disorders. In: Hand MS, Thatcher CD, Remillard RL, Roudebush P, Novotny BJ, eds. Small Animal Clinical Nutrition. 5th ed. Topeka, KS: Mark Morris Institute; 2010:637–665.
8. Akucewich L, Roudebush P, Jackson HA. Nutrient-responsive dermatoses. In: Jackson HA, Marsella R, eds. BSAVA Manual of Canine and Feline Dermatology. Quedgeley, UK: BSAVA; 2012:227–234.