Medical management of perianal fistula
Feb 01, 2003
Treatment has historically been surgical debridement combined with long courses of antibiotics. Results were often disappointing with a high recurrence rate, and, occasional complications such as fecal incontinence or anal stricture.
Based on a positive response to many dogs to immunosuppressive drug, an immunologic basis for the disease is now suspected. In 1996 a study described 27 dogs given prednisone and a novel protein diet. The prednisone dose (plus antibiotics) given was 1 mg/lb/day for two weeks, then 0.44 mg/lb/day for another four weeks, then 0.44 mg/lb every other day (adjusted as necessary to keep fistulation to a minimum). The outcome was complete resolution in one-third, partial resolution in one-third and no improvement in one-third of the dogs (Harkin et al., "Association of perianal fistula and colitis in the German Shepherd dog; response to high-dose prednisone and dietary therapy," JAAHA, 32(6), Nov.-Dec. 1996).The 1997 study of 20 dogs treated with cyclosporine was reported. By 16 weeks, fistulae were completely healed in 85 percent. Fistulae recurred between two and 24 weeks after the drug was discontinued. However in seven out of 17 dogs, no prognostic factors for recurrence were identified except mean duration of fistulae before treatment was significantly longer for dogs that developed recurrence (12.8 months, range one-36 months) than for dogs that did not (5.1 months, range one-18 months). The mean dose used for cyclosporine was 5.5 mg/kg PO BID, with a range of 4.8 to 6-8, mg/kg BID. Mean +/- S.D. trough blood concentration was 507+/-307 ng/ml. (Mathews, et al, "Randomized Controlled Trial of Cyclosporine for Treatment of Perianal Fistulas in Dogs," JAVMA, 211 (10), Nov. 15, 1997).
Since the original study, 50 more dogs were treated by this same group, using lower doses of cyclosporine (1.75-3.0 mg/kg BID, blood concentrations of 100-300 ng/ml). These doses were also effective. The authors recommend dogs are treated for as long as there is progressive improvement and for four additional weeks after all fistulae appear completely healed.
A small study of five dogs treated with azathioprine and metronidazole described all dogs improved, typically reaching a plateau four to six weeks after beginning treatment. All dogs still required surgical intervention to remove anal glands (four dogs) and/or residual fistulae (five dogs), but it was concluded that the use of the medical treatment followed by surgery minimized potential morbidity associated with the aggressive use of either medical or surgical treatment alone. (Tisdall, et al., "Management of perianal fistulae in five dogs using azathioprine and metronidazole prior to surgery," Aust Vet J, 77(6), June 1999).
A 2000 study of the effect of topical tacrolimus in 10 dogs (Misseghers et al., "Clinical observations of the treatment of canine perianal fistulas with topical tacrolimus in 10 dogs" Can Vet J, 41(8), August 2000), daily gentle cleansing of the perianal skin followed by a thin film of 0.1 percent tacrolimus ointment was applied over the entire perianal skin; the volume of ointment used was thus empirical. After 16 weeks, five showed complete resolution, four showed partial resolution and one showed no improvement. Four of the five dogs with less than complete resolution were sexually intact (three females, one male). The authors recommend that neutering be done in conjunction with immunotherapy. This seems to improve response.
Although 10 to 100 times more potent, tacrolimus and cyclosporine act similarly, blocking early events in T lymphocyte differentiation. Tacrolimus is effective in the treatment of dermatoses without affecting the systemic immune system, while cyclosporine won't work for dermatoses unless immunosuppressive levels are achieved. Therefore, systemic side effects can be avoided, costs reduced and higher drug concentration achieved locally with topical tacrolimus. Systemic cyclosporine costs can be substantial; including the cost of the drug itself and the cost of monitoring blood levels to ensure an adequate, but not excessive, concentration of drug. Costs can be reduced by using concurrent ketoconozole, which acts to inhibit cyclosporine clearance; cyclosporine dose may be reduced by as much as 80 to 90 percent when ketoconazole is used (Mouatt, JG "Cyclosporin and ketoconazole interaction for treatment of perianal fistulas in the dog," Aust Vet J 80(4), April 2002).
Surgical management may still be necessary if there is incomplete resolution of the fistulae, anal gland involvement or extensive fibrosis, but initial medical management is an excellent first approach. In many cases, medical management will resolve the problem completely, but if surgery is still required, it will often be less extensive with less chance of complications.