I. The Use Of Lufenuron For Dermatophytosis

Lufenuron is from the class of benzoylurea insecticides that have been used in agriculture to control insect pests. Lufenuron (Program) was developed for use in dogs and cats for control of fleas because it inhibits development of fleas by inhibition of chitin synthesis, polymerization, and deposition. It exhibits a long-lasting effect after a single administration because it is a highly lipophilic compound that persists in skin of animals. Recently, lufenuron has been discovered to produce an antifungal effect as well, because fungal cell walls also contain chitin. In the initial report (1), the authors showed that doses ranging from 51-266 mg/kg, and 47-68 mg/kg in cats and dogs, respectively, controlled dermatophyte infections. After a single dose, remission of clinical signs occurred in approximately 10-15 days and 16-25 day for cats and dogs, respectively. A follow-up report by the authors (2) suggests that in catteries, the low dose has failed and a higher dose of 100 mg/kg for cats is recommended. They also recommend that the entire cattery be treated to eliminate carriers and monthly treatments should be considered. For dogs, a minimum dose of 80 mg/kg is recommended. These dose ranges are higher than the dose used to treat fleas (30 mg/kg and 10 mg/kg for cats and dogs, respectively) but below the toxic range reported by the manufacturer. Because lufenuron is a highly lipophilic drug, administration with a meal will enhance oral absorption. In a limited number of cases at UC-Davis, the efficacy has been variable; it is possible that some treatment failures especially in multi-animal households may be due to failure to give the medication with a meal.

II. Cyclosporine For Atopic Dermatitis And Other Diseases

Cyclosporine (Neoral, Atopica: Novartis) binds to specific intracellular receptors in T-lymphocytes. Cyclosporine produces a specific effect without inhibiting nonspecific immunity or causing myelosuppression. Cyclosporine has been used for a number of diseases in veterinary dermatology. In dogs, when used in the treatment of perianal fistulas, (3,4) an approximate 80% healing rate was found (2.5-6 mg/kg/day); in sebaceous adenitits, good response was reported in one case (5); and in idiopathic sterile nodular panniculitis, excellent results were seen in 2 reported cases which were followed for 6 months following discontinuance of the cyclosporine (6). However, in small pilot studies, results for treating pemphigus foliaceous in dogs have been disappointing (7).

The use of cyclosporine for treating canine atopic dermatitis (CAD) has been investigated in dogs (8-10). In several studies, the efficacy of cyclosporine in controlling clinical signs of CAD was equal to that of corticosteroids. The author has been impressed with the rapidity (within 2-4 weeks) and degree (decrease of >80% pruritus) of the response in some dogs. Dosages of 5 mg/kg/day are recommended.

Cyclosporine is well-tolerated in cats and has been investigated for treating skin diseases. A good response to a dose of 25 mg/cat was seen in 6 cases of eosinophilic plaque and 3 cases of oral eosinophilic granuloma (11). In three cases of indolent lip ulcers, the response was less impressive.

Anecdotally, the disease entity being termed feline atopic dermatitis also seems to respond to this drug at a dose of 7 mg/kg/day. Also anecdotally (from Vet Derm Listserv) it has been successful in treating cases of idiopathic facial dermatitis of Persian cats, at doses of 5 mg/kg q 24-48 hr.

Cyclosporine is available as a 100mg/ml solution, and 25 mg and 100 mg gel caps. Ideally, this should be given on an empty stomach, but if this causes GI upset, administration with food may help. It is remarkably well-tolerated in animals. Because low doses are used for treating perianal fistulas and atopic dermatitis, usually 5 mg/kg/day or less, adverse effects in dogs are uncommon. The most common problem is nausea and loss of appetite.

Because cyclosporine undergoes complicated metabolism in the intestine and liver, enzyme systems can be turned on (induced) or turned off (inhibited) by other drugs to alter the amount of cyclosporine absorbed. Inducing drugs include rifampin and may decrease the extent of cyclosporine. Inhibiting drugs include ketoconazole, erythromycin, and in people, flavonoids from grapefruit juice. Cimetidine does not affect metabolism. Because ketoconazole will reduce cyclosporine clearance in dogs by as much as 85%, cyclosporine doses can be reduced if a patient is also receiving ketoconazole(5-10mg/kg).

III. Pentoxifylline and Ischemic Dermatopathies

Pentoxifylline (PTX)is from the group of drugs called methylxanthines. PTX is derived from theobromine. Pentoxifylline, and other methylxanthines produce anti-inflammatory effects. PTX also improves blood flow through narrowed arteries because of the rheological property in which it allows red blood cells to change shape. It is not known if the improvement in patients with ischemic dermatoses are caused by improved blood flow (rheological effect), or via the antiinflammatory mechanisms.

PTX was first used in veterinary dermatology for familial canine dermatomyositis (FCD)(12) and contact allergy (13). More recently, it has been put forth as a treatment for atopic dermatitis (14) and erythema multiforme (EM).

In a clinical report in which PTX was used successfully to treat atopic dermatitis in dogs, the dose used was 10 mg/kg q12h, orally, although there was still some pruritus at 28 days of treatment (14). However, the results of pharmacokinetic studies showed that the half-life in dogs is short, < 30 minutes, with only 30% oral absorption (15). Therefore, it is possible that improved efficacy might be possible if administered more frequently: Some veterinarians now give PTX to dogs at doses as high as 20-30 mg/kg q8h, orally.

Pentoxifylline is available in a 400 mg tablet. Some veterinarians use dosing regimens that allow the use of a full tablet for a large-size dog. When tablets are broken or crushed for cats (e.g., 100 mg per cat) the taste is very unpleasant. Other side effects in dogs and cats include vomiting, nausea, excitement, and 'nervousness'. The author has not seen as much problem with vomiting as initially reported, perhaps due to insistence on giving the drug with food. The author has seen 2 dogs which developed erythema multiforme (confirmed on histopathology) due to pentoxifylline.

The efficacy of PTX at UC-Davis has varied. It appears to have worked well in many cases of FCD, reasonably well in some cases of non-FCD ischemic dermatitis, and rather variably in vasculitis, EM, or atopic dermatitis.

IV. Infiltrative Mural Folliculitis (Lymphocytic Mural Folliculitis)in Cats

Not a disease but rather a histologic presentation which can be caused by at least 6 different etiologies. Physical presentation is variable but most often there is partial to complete alopecia with dense fine adherent scale of the head and neck with lesser involvement of the remainder of the body. The unifying feature is a lymphohistiocytic infiltration of the outer root sheath of the hair follicle, generally at and above the level of the follicular isthmus. The pathogenesis is suspected to be an inappropriate immunologic attack directed at cells of the outer root sheath.

Six types of infiltrative mural folliculitis are recognized:

1.  Dermatophyte-associated: Dermatophyte organisms may be visible histologically, but not always. Disease is suspected by histologic pattern, subsequent positive dermatophyte culture, and response to antifungal therapy.

2.  Sebaceous Adenitis: Histologic features similar to dogs: most remarkable finding is absence of sebaceous glands. Cats with sebaceous adenitis are healthy despite a scaly alopecic dermatitis and may spontaneously recover (16).

3.  Pseudopelade-like: A rare immune-mediated alopecia in humans due to immune mediate destruction of the mid-follicle region(17). Rare.

4.  Mild idiopathic: Mild lesions but consistent with this pattern. Cats may have localized or generalized disease, spontaneous recovery or rapid response to steroid therapy.

5.  Mucinotic degenerative (severe idiopathic): This form has extensive skin disease and histopathologic changes. Cats with this form are middle aged to old; lesions are diffuse scaly alopecia with concurrent lethargy, depression, and/or dehydration. The skin on the head of affected cats seems tight as if it has been infiltrated giving the cat a distinctive furrowed brow and swollen or slanted eyelids. Complete physical and laboratory evaluation (clinical pathology and ultrasound) is indicated but may not be informative. Treatment has not been well-defined, and these cats may be euthanized due to ongoing nature of illness (18). Interestingly, two cats have had resolution of signs when fed restricted novel diets (19).

6.  Early/prodromal feline epitheliotropic T-cell lymphoma may appear as a lymphocytic mural folliculitis, thus this disease must be considered in older cats with mural folliculitis. Sequential biopsies over time may be required before this neoplastic process becomes evident.

References

1.  Ben-Ziony Y, Arzi B. Use of lufenuron for treating fungal infections of dogs and cats: 297 cases (1997-1999). J Am Vet Med Assoc 2000; 217:1510-3.

2.  Ben-Ziony Y, Arzi B, Tivon K. Updated information for treatment of fungal infections in cats and dogs. J Am Vet Med Assoc 2001; 218:1718 [letter].

3.  Mathews KA, Sukhiani HR. Randomized controlled trial of cyclosporine for treatment of perianal fistulas in dogs. J Am Vet Med Assoc 1997; 211:1249-53.

4.  Patricelli AJ, Hardie RJ, McAnulty JE. Cyclosporine and ketoconazole for the treatment of perianal fistulas in dogs. J Am Vet Med Assoc 2002;220:1009-16.

5.  Carothers MA, Kwochka KW, Rojko JL. Cyclosporine-responsive granulomatous sebaceous adenitis in a dog. J Am Vet Med Assoc 1991; 198:1645-8.

6.  Guaguère E. Efficacy of cyclosporin in the treatment of idiopathic sterile nodular panniculitis in two dogs (Abstr). Vet Dermatol 2000; 11 (Supplement 1): 26.

7.  Olivry T, Rivierre C, Murphy KM. Efficacy of cyclosporine for treatment induction of canine pemphigus foliaceus. Vet Rec 2003;152:53-4.

8.  Olivry T, Steffan J, Fisch RD, et al. Randomized controlled trial of the efficacy of cyclosporine in the treatment of atopic dermatitis in dogs. J Am Vet Med Assoc 2002;221:370-7.

9.  Olivry T, Rivierre C, Jackson HA, et al. Cyclosporine decreases skin lesions and pruritus in dogs with atopic dermatitis: a blinded randomized prednisolone-controlled trial. Vet Dermatol 2002;13:77-87.

10. Steffan J, Alexander D, Brovedani F, et al. Comparison of cyclosporine A with methylprednisolone for treatment of canine atopic dermatitis: a parallel, blinded, randomized controlled trial. Vet Dermatol 2003; 14: 11-22.

11. Guaguère E, Prélaud P. Efficacy of cyclosporin in the treatment of 12 cases of eosinophilic granuloma complex (Abstr). Vet Dermatol 2000; 11 (Supplement 1): 31.

12. Hargis AM, Mundell AC. Familial canine dermatomyositis. Compendium of Continuing Education for the Private Practitioner 1992; 14: 855-865.

13. Marsella R, Kunkel GA, Lewis DT. Use of pentoxifylline in the treatment of allergic contact reactions to plants of the Commelinceae family in dogs. Vet Dermatol 1997; 8:121-126.

14. Marsella R, Nicklin CF. Double blinded placebo controlled cross over study on the affects of pentoxifylline in canine atopy. Vet Dermatol 2000; 11: 255-260.

15. Marsella R, Nicklin CF, Munson JW, et al. Pharmacokinetics of pentoxifylline in dogs after oral and intravenous administration. Am J Vet Res 2000; 61:631-7.

16. Baer K, Shoulberg N, Helton K. Sebaceous adenitis-like disease in two cats (Abstract). Vet Path 1993; 30:437.

17. Olivry T, Power HT, Woo JC, et al. Anti-isthmus autoimmunity in a novel feline acquired alopecia resembling pseudopelade of humans. Vet Dermatol 2000; 11: 261-270.

18. Gross TL, Olivry T, Vitale CB, et al. Degenerative mucinotic mural folliculitis in cats.Vet Dermatol 2001;12:279-83.

19. Declercq J. A case of diet-related lymphocytic mural folliculitis in a cat. Vet Dermatol 2000; 11: 75-80.