Retinoids

Naturally occurring and synthetic compounds with vitamin A activity include retinol, retinoic acid, and retinol derivatives or analogs. At the molecular level, retinoids are important in regulation of proliferation, growth, differentiation, and maintenance of epithelial tissues. Retinoids also affect proteases, biosynthesis of mucopolysaccharides, prostaglandins, cellular adhesion, cellular communication, and immunity. They prevent tumor promotion by inhibition of ornithine decarboxylase, a key enzyme for cell proliferation and differentiation. Vitamin A (1,000 IU/kg) has been used for follicular keratosis in cats. However, the retinoids used most commonly are isotretinoin (13-cis-retinoic acid) and etretinate (no longer available but replaced with acitretin, a metabolically active metabolite of etretinate).

Isotretinoin is indicated for Schnauzer comedo syndrome, ichthyosis, feline acne, sebaceous adenitis, epitheliotropic lymphoma, keratoacanthoma, and sebaceous gland hyperplasias and adenomas. The dosage is 1–3 mg/kg, sid. Adverse effects include conjunctivitis, mucocutaneous drying, alopecia, pruritus, hyperactivity, vomiting, and diarrhea. In dogs, blood chemistry increases not normally associated with clinical disease include plasma cholesterol, triglycerides, ALT, AST, and alkaline phosphatase. Rarely, keratoconjunctivitis sicca may develop in dogs. Conjunctivitis, anorexia, diarrhea, and vomiting are the major side effects in cats. All retinoids are potent teratogens, and teratogenicity may persist for up to 2 yr after treatment with etretinate because the half-life is ~100 days. Skeletal abnormalities that may be seen with longterm therapy, including premature closure of the epiphyses in growing animals, cortical hyperostosis, periosteal calcification, and long-bone demineralization, are less common with etretinate than with isotretinoin. Monitoring during longterm therapy should include complete physical examinations and serum chemistry profiles at monthly intervals for the first 3–4 mo and then every 4–6 mo.

Zinc

Zinc is an important factor of many enzyme systems and is necessary for maintenance of growth, metabolism, normal reproduction, and hormonal regulation. It is essential for keratinization and immune function. Zinc supplementation is given in cases of insufficient intestinal absorption, including deficiency syndrome I (Siberian Huskies, Alaskan Malamutes) and syndrome II (rapidly growing dogs on zinc-deficient diets). Dietary deficiency may be either absolute or relative—diets high in phytates or minerals may inhibit zinc absorption. For syndrome I, zinc supplementation is given at 1 mg elemental zinc/kg, PO, sid (10 mg zinc sulfate/kg, 5 mg zinc gluconate/kg, or 1.7 mg zinc methionine/kg). Supplementation is typically lifelong. If the response is insufficient after 4 wk, the dose should be increased by 50%. Low-dose corticosteroids may also enhance zinc absorption through induction of metallothionein in some nonresponsive cases. Animals with syndrome II normally respond to correction of the diet with resolution within 2–6 wk, although supplementation speeds this process.

Hereditary zinc deficiency associated with deficient intestinal absorption has also been reported in Friesian, Danish Black Pied, and Shorthorn cattle. There is a rapid response to zinc oxide given at 0.5 g, PO, sid, or zinc sulfate at 2 g, PO, given weekly. Response to zinc supplementation is usually rapid (a few days) except for cases of achromotrichia, which requires several weeks for resolution.

Last full review/revision March 2012 by Michael Shipstone, BVSc, FACVSc, DACVD