What's new in dermatologic therapy?

Five new drugs show promise in treating dermatomyositis, atopic dermatitis, papillomavirus infection, and more. Find out if they should be in your treatment arsenal.
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Jun 01, 2007

Dermatologic problems can be frustrating to treat. Pentoxifylline, tacrolimus, pimecrolimus, interferon, and imiquimod offer potential new therapeutic options. Although few veterinary studies showing positive results with these drugs are available, veterinary dermatologists have been using them with varying degrees of success. This article highlights what has worked for us and other veterinary dermatologists and discusses the results of drug studies.

PENTOXIFYLLINE


Figure 1. A dog with dermatomyositis. Note the alopecia, hyperpigmentation, and scarring on the front limbs, muzzle, and periocular region.
Pentoxifylline is a member of a class of drugs that inhibit phosphodiesterase (PDE) enzymes, referred to as PDE inhibitors. Pentoxifylline makes red blood cells more pliable and decreases blood viscosity. It also decreases fibronectin, reduces the production of cytokines (tumor necrosis factor-alpha, interleukin-1, interleukin-6, interleukin-8), decreases leukocyte response to interleukin-1, impairs t lymphocyte binding to keratinocytes, decreases fibroblast activity, and, with long-term use, may decrease fibrosis.1,2








Figure 2. The same dog as in Figure 2 four months after beginning pentoxifylline therapy. Note the resolution of the lesions.
Pentoxifylline is beneficial in treating a variety of canine skin diseases.3-5 Its effectiveness may be due to any one or a combination of its different actions on the immune response. Pentoxifylline has been evaluated most thoroughly in well-designed studies for treating atopic dermatitis3 and has been reported effective in treating dermatomyositis4 (Figures 1 & 2) and contact dermatitis.5

Veterinary dermatologists have also recommended pentoxifylline to treat vasculitis, ischemic dermatopathy, pinnal thrombovascular necrosis, idiopathic mucinosis, and erythema multiforme and as an adjunctive therapy for idiopathic onychomadesis, immune-mediated dermatoses, fibrosing deep pyoderma, and pododermatitis. However, studies supporting pentoxifylline's efficacy in treating these conditions are lacking. For example, only one of seven dogs with cutaneous vasculitis exhibited a definitively favorable response to pentoxifylline treatment,6 and only two of five dogs with lupoid onychodystrophy showed excellent treatment responses.7 Poor responses were seen in four of four dogs with vesicular cutaneous lupus erythematosus treated with pentoxifylline alone or in combination with other drugs.8

Initially, many veterinary dermatologists administered 10 mg/kg pentoxifylline orally two or three times a day. It has been suggested that a frequency of three times a day might be preferable for some diseases, such as atopic dermatitis.9 In addition, some veterinary dermatologists have reported doses of 15 to 25 mg/kg to be more effective than 10-mg/kg doses. One study showed a good response in 10 of 10 dogs with dermatomyositis at an average dosage of 25 mg/kg (range 18 to 31 mg/kg) given orally twice a day. The median response time was six weeks with a range of four to 10 weeks.4

A pharmacokinetic study in dogs showed that after a single oral dose of 30 mg/kg pentoxifylline, plasma pentoxifylline concentrations reached 1,000 ng/ml (the therapeutic concentration in people) and persisted for 510 minutes (± 85 min), suggesting that twice-a-day administration may be effective at that dose.10 However, one caution is that bioavailability varied from about 25% to 75%.10 In contrast, another study in dogs showed that 15 mg/kg given orally three times a day produced plasma concentrations equivalent to therapeutic concentrations in people.11

The efficacy of generic pentoxifylline is uncertain. No comparative studies exist, but some veterinary dermatologists report better responses to the brand name formulation Trental (Sanofi-Aventis).

No serious adverse effects of pentoxifylline have been reported with any frequency in dogs. Vomiting and diarrhea are the major concerns in dogs and are dose-related in people. Two dogs receiving pentoxifylline reportedly developed erythema multiforme12 ; however, one author (Griffin) has used it to treat erythema multiforme with some cases showing a beneficial effect.