No studies have evaluated the use of pentoxifylline in cats. However, veterinary dermatologists have used it for atopic dermatitis,
ischemic dermatopathy, and nonhealing deep bacterial infections in cats at doses of 100 mg given orally twice a day or 10
mg/kg given orally twice a day with variable success and no observed adverse effects.
Tacrolimus, a macrolide produced by Streptomyces tsukubaensis, is available in oral and injectable formulations (Prograf—Astellas Pharma) and has been used extensively as an immunosuppressive
in human transplant patients. Side effects from the systemic use of tacrolimus (Prograf) in dogs are severe and preclude systemic
use of this drug in dogs; these side effects include weight loss, vomiting, and diarrhea.13 Protopic (Astellas Pharma), a topical formulation available as a 0.1% ointment, was the first Food and Drug Administration
(FDA)-approved topical immunomodulator. These drugs have topical anti-inflammatory effects without the cutaneous atrophy-inducing
and metabolic effects of topical glucocorticoids.
Tacrolimus was recently approved for treating atopic dermatitis in people and is also beneficial in treating psoriasis and
possibly alopecia areata. Large multicenter clinical studies in people indicate that it is a safe drug with minimal systemic
absorption. Its mechanism of action is similar to cyclosporine's, but tacrolimus is 10 to 100 times more potent. It works
by calcineurin inhibition, resulting in suppression of antigen-presenting T cells, inhibition of the production of multiple
cytokines from T cells (interleukin-2, interleukin-3, interleukin-4, interferon, granulocyte-macrophage colony-stimulating
factor, and tumor necrosis factor), down regulation of cytokine expression in other cells (mast cells, basophils, eosinophils,
keratinocytes, and Langerhans cells), and inhibition of eosinophil recruitment.14
Topical tacrolimus has been reported to be effective in treating canine perianal fistulas (Figure 3), although it is less effective than systemic cyclosporine.15 It is used to maintain control of perianal fistulas once a sufficient response to cyclosporine occurs. It also reduces the
severity of localized skin lesions of canine atopic dermatitis16,17 and may be useful in treating localized lesions associated with discoid lupus erythematosus and pemphigus foliaceus.18 Veterinary dermatologists have used it for a variety of veterinary dermatologic diseases in which lesions are localized,
and one author (Griffin) has used the topical formulation to treat alopecia areata and vitiligo.
Figure 3. A perianal fistula in a dog.
For both tacrolimus and pimecrolimus (discussed below), the FDA has issued a public health advisory warning of a potential cancer risk based on information from animal studies
and case reports in a small number of patients. In the authors' practice, clients are advised of this warning and are advised
to wear gloves when applying these drugs. No studies evaluating this potential cancer risk in dogs and cats have been conducted.
Pimecrolimus (Elidel—Novartis) is an ascomycin macrolactam derivative that acts similarly to tacrolimus, although a recent
study showed that it exerts a more selective immunomodulatory effect.19 In mice, pimecrolimus effectively inhibited the secondary elicitation phase that is the clinical manifestation of contact
hypersensitivity, but it did not impair the primary immune response, or sensitization phase, in contrast to tacrolimus and
cyclosporine.19 No studies comparing pimecrolimus and tacrolimus use in dogs have been done, but veterinary dermatologists report that the
efficacy of pimecrolimus is similar to or less than that of tacrolimus.
Table 1 Five Selected New Drugs Used in Veterinary Dermatology
Interferons are a group of glycoprotein cytokines produced by a variety of inflammatory cells and fibroblasts that have numerous
immunologic effects, including antiviral, antiproliferative, and immunomodulatory activities. Several recognized interferons
exist, and they vary in their immunologic effects. Their main uses are based on interferon's antiviral and antineoplastic
properties, but they may also be beneficial in treating a variety of dermatologic disorders.