VIN Clinical Q&A: How useful is topical tacrolimus in treating perianal fistulas?

Q: How much success have you had using topical tacrolimus as a single agent once or twice a day to treat perianal fistulas? I have a client who is reluctant to give his dog cyclosporine and ketoconazole because of the cost and because I can't promise a lifelong cure. Also, are you seeing good results with the cyclosporine-ketoconazole combination?

Stephen Lee Jr., DVM

37193 Longwood Ave.

Prairieville, LA 70769

A: At The University of Tennessee, we have had good success treating perianal fistulas with topical tacrolimus (Protopic 0.1%—Fujisawa Healthcare) applied twice a day until the lesions resolve, then tapered to the lowest frequency that controls the inflammation (usually every two or three days).1 Tacrolimus is a macrolide immunosuppressant that inhibits T-lymphocyte activation. It penetrates the skin better than topical cyclosporine does.2

Tacrolimus costs about $70 for a 30-g tube, so sticker shock can be a problem. Since only enough ointment is needed to cover the lesions, the 30-g tube usually lasts one to three months. Owners should use a cotton-tipped applicator or gloves to avoid contacting the ointment. In people with atopic dermatitis, a mild burning sensation has been reported; however, the patients I have treated for perianal fistulas have not demonstrated any adverse reactions.

1. A 5-year-old, spayed female German shepherd with severe perianal fistulas.

For severe cases, we initially give either high-dose prednisolone or cyclosporine, in combination with topical tacrolimus to control the lesions (Figures 1 & 2). Either prednisolone or cyclosporine works well. Prednisolone (0.75 to 1 mg/lb/day orally for two or three weeks; taper the dose over two or three months) is cheaper than cyclosporine but has more side effects. Owners who give cyclosporine (5 mg/kg/day orally on an empty stomach; taper the dose to every other day after six to eight weeks of therapy or when 80% resolution occurs) are usually pleased despite the higher cost.

2. The same dog as in Figure 1 after immunosuppressive systemic and topical treatment. Note the change in normal anal structure and the persistent mild inflammation requiring maintenance topical treatments.

I often use ketoconazole (5 to 10 mg/kg/day orally) in conjunction with the cyclosporine because it speeds resolution and allows me to taper the cyclosporine dose more rapidly.3 Ketoconazole inhibits the cytochrome P-450 liver enzyme system, thereby increasing therapeutic blood concentrations of cyclosporine. Some dermatologists will reduce the dose of cyclosporine by as much as 50% when ketoconazole therapy is added. I prefer to administer the higher dose to achieve maximal response in the shortest time and then taper the dose and frequency of administration.

Most patients respond well and can be tapered off the systemic treatments and maintained on alternate-day topical tacrolimus therapy. Occasionally, a small residual nonhealing lesion will persist despite prolonged treatment. The wound-healing process can be reinitiated in these cases by débriding the lesion by using scalpel, laser, cryosurgery, or cautery techniques. In cases that are refractory to immunosuppressive therapy with systemic and topical treatments, aggressive surgical intervention may be needed.

It is important to stress that perianal fistula is a controllable disease rather than a curable one. If the inflammation remains controlled and the lesions shrink but a chronic nonhealing wound remains, we use laser therapy to promote healing. And, of course, every affected patient participates in a food trial.

Keith A. Hnilica, DVM, MS, DACVD

Department of Small Animal Clinical Sciences

College of Veterinary Medicine

The University of Tennessee

Knoxville, TN 37996

REFERENCES

1. Misseghers, B.S. et al.: Clinical observations of the treatment of canine perianal fistulas with topical tacrolimus in 10 dogs. Can. Vet. J. 41 (8):623-627; 2000.

2. Gianni, L.M.; Sulli, M.M.: Topical tracrolimus in the treatment of atopic dermatitis. Ann. Pharmacother. 35 (7-8):943-946; 2001.

3. Patricelli, A.J. et al.: Cyclosporine and ketoconazole for the treatment of perianal fistulas in dogs. JAVMA 220 (7):1009-1016; 2002.