pfmedic/surg

PERIANAL FISTULA IS A MEDICAL (NOT A SURGICAL) PROBLEM
Richard Walshaw, BVMS, Diplomate ACVS,
College of Veterinary Medicine,Michigan State University, East Lansing, MI

Perianal fistula is a chronic inflammatory, ulcerative disease of the perianal tissues that is seen almost exclusively in the German Shepherd dog. The exact etiology of this disease has not been determined as evidenced by the failure of studies that have been performed to investigate a possible immunological, bacterial, endocrine, or anatomic basis for the disease. Consequently, although many different treatment methods have been proposed for this problem, none of those reported are routinely successful in controlling the disease.

Previously reported medical management of perianal fistula has included cleansing the affected area, topical administration of antibiotic and steriod preparations, and the use of tail braces in combination with topical antiseptic and systemic antibiotic therapy. Generally, medical management to this point has been considered to be palliative at best plus it has been suggested that it many be detrimental as it delays surgical intervention.

Historically many different surgical procedures have been described in the veterinary literature for the treatment of perianal fistula. Chronologically, these have included surgical excision, chemical cautery, cryosurgery, tail amputation, electosurgery, and laser surgery. All of these surgical procedures have, to some degree, been associated with significant postoperative complications, for example, recurrence, anal stricture formation, fecal incontinence, tenesmus and dyschezia and none of them can be considered to be 100% successful at controlling this disease process.

A number of years ago a German Sherherd dog was presented to Michigan State University for treatment of perianal fistula. During the work-up of this patient it was also discovered that the dog had multicentric lymphosarcoma. Multi-drug chemotherapy was initiated to treat the lymphosarcoma. Within 4 weeks of chemotherapy it was noted that the perianal fistula problem had completely resolved. The response seen in this dog stimulated Dr. Ken Harkin and myself to think about whether perianal fistula was, in fact, just an external manifestation of a systemic disease. The German Shephered breed, besides being uniquely affected with perianal fistula, also has a significant problem with infiltrative/inflammatory bowel dieseases, particularly affecting the colon and rectum. Therefore a prospective study was initiated to investigate the possible association between perianal fistula and colitis/proctitis in the German Shepherd dog and to evaluate the response of perianal fistula to high dose prednisone and an alternative protein diet. The results of this prospective clinical trial have been published and can be summarized as follows:

1. A majority of the dogs had clinical signs that could be attributable to either perianal fistula and/or infiltrative/inflammatory large bowel diesase.

2. All of the dogs had histologic evidence of mild, severe, chronic, infiltrative/inflammatory large bowel disease on biopsy specimens obtained by colonoscopy/proctoscopy.

3. Inflammatory cell infiltration in the biopsy specimens was composed predominantly of plasma cells and lymphocytes, with eosinophilic infiltration being present in 25% of the cases.

4. In general, there was no significant histopathologic improvement in the post-treatment biopsies when compared to the initial biopsies apart from the substantial decrease in the eosinophilic component when present.

5. The treatment protocol resulted in the following response:

-1/3 of the dogs had complete resolution of the perianal fistula lesions and clinical signs.

-1/3 of the dogs has resolution of the clinical signs and significant improvement/stabilization of the perianal fistula lesions.

-1/3 of the dogs had little or no improvement of clinical signs or perianal lesions.

The findings from this study raised the following points and questions:

1. The results tend support the concept that perianal fistula is not an independent disease entity but is , in fact an external manifestation of a systemic process, namely infiltrative/inflammatory large bowel disease. A similar problem is seen in humans with Crohn's disease who can develop anal fistulae.

2. Perianal fistula may well be an immunologically mediated disease. A food allergy component may need to be considereed as an underlying cause.

3. It is known that improvement in clinical signs associated with infiltrative/inflammatory large bowel disease can occur without histologic improvement on biopsy. This suggests that the underlying disease is not cured but only kept under control. The implication of this is that German Shepherds with perianal fistula need to be followed over a long period as relapse is possible. This can be seen clinically, for example, where a dog is free of disease for over two years and then relapses.

4. Could the results of treatment be iproved by more aggresively treating the chronic infiltrative/inflammatory large bowel disease, as is done for patients presenting with only colitis?

An attempt is being made to answer the points and questions raised by this first clinical study at Michigan State University, Veterinary Teaching Hospital and Ontario Veterinary College, University of Guelph.

Ongoing Clinical Study, Michigan State University For the past one and one half years the following protocol has been used for all German Shepherd dogs presenting to Michigan State University for the treatment of perianal fistula:

1. Diet:
Dogs are placed on a strict alternative protein/hypoallergenic diet. The diet that is currently recommended is Eukanuba Response Formula FP (Iams Co.). This is a fish and potato based diet. An equivalent home-cooked diet could also be used. The dogs are not allowed any meat or meat by-product containing foods. Any snack type foods must be non-meat containing, for example, vegetables. The dogs remain under strict dietary control for life.

2. Sulfasalazine:
Sulfasalazine, 1gm., 3 times daily, orally, for at least 4 months (at least 1 month after the cessation of prednisone therapy). Length of therapy depends upon the resolution of the lesions.

3. Prednisone:
Prednisone, 0.5mg/#, once daily, orally, for at least 4 weeks. Treatment at this dose is extended if lesions have not resolved. Prednisone dose is decreased to 0.25mg/#, once daily, orally, for 6-8 weeks. Length of therapy depends upon resolution of the lesions.

4. Follow-Up Evaluations:
All dogs are seen at monthly intervals until there is complete resolution of the disease. At the time of re-evaluation the drug therapy may be adjusted depending upon the progress of the patient. After the disease has completely resolved, the dogs are followed by periodic telephone contact with the owners.

Initial Results:
Since the initiation of this clinical study, no dogs presented with perianal fistula have had surgery for their disease. All of the dogs have had complete resolution of their clinical signs and the vast majority have had complete healing of the perianal lesions. A few dogs have small, persistent, quiescent perianal lesions that are stable. A few dogs have had relapse of the disease as they were tapered off the prednisone. In these dogs, increasing the prednisone dose and extending the period of administration has resulted in healing of the perianal lesions. As this is an ongoing clinical study, long term results are not available at this time.

Cyclosporin Treatment Of Perianal Fistula, Ontario Veterinary College:

Cyclosporin has been shown to be of benefit in the treatment of anal fistulae associated with Crohn's disease in humans. Because of this a clinical study was initiated to evaluate the efficacy of cyclosporin treatment for perianal fistula in the German Shepherd dog. This was a prospective, randomized, double-blind, controlled study.

Initial results after 4 weeks, showed a significant resolution of the disease in the cyclosporin treated dogs when compared to the placebo treated controls. After 4 weeks, the placebo treated dogs were switched to cyclosporin therapy and demonstrated marked resolution of thier disease.

Conclusions of the study were that cyclosporin had a dramatic beneficial effect on perianal fistula in the German Shepherd dog.

The results of these two ongoing studies add further evidence to support the theory that perianal fistula in the German shepherd dog is an immune mediated disease as both treatment protocols are directed toward suppression and/or modification of the immune response. Long term follow-up needs to be completed to see if it is possible to keep the disease under control by, for example strict dietary control, or will periodic flare ups occur that need aggressive therapy, as is seen with colitis patients.

References
1. Harkin,KR, Walshaw, R at al Association of perianal fistula and colitis in the German Shepherd dog: response to high-dose prednisone and dietary therapy. JAAHA, 32: 515-520, 1996. 2. Matthew, KA and Sukhiani, HR OI 27-400 (Cyclosporin) treatment of canine perianal fistulas: A prospective, randomized, double-blind, controlled study. p16. Proceedings, 31st Annual Meeeting, ACVS, 1996.

unable to contact author

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Sulfasalazine is used to treat bowel inflammation, diarrhoea (stool frequency), rectal bleeding, and abdominal pain in patients with ulcerative colitis, a condition in which the bowel is inflamed. Sulfasalazine is in a class of medications called anti-inflammatory drugs. It works by reducing inflammation (swelling) inside the body.

Prednisone is used alone or with other medications to treat the symptoms of low corticosteroid levels (lack of certain substances that are usually produced by the body and are needed for normal body functioning). Prednisone is also used to treat other conditions in patients with normal corticosteroid levels. These conditions include certain types of arthritis; severe allergic reactions; multiple sclerosis (a disease in which the nerves do not function properly); lupus (a disease in which the body attacks many of its own organs); and certain conditions that affect the lungs, skin, eyes, kidneys blood, thyroid, stomach, and intestines. Prednisone is also sometimes used to treat the symptoms of certain types of cancer. Prednisone is in a class of medications called corticosteroids. It works to treat patients with low levels of corticosteroids by replacing steroids that are normally produced naturally by the body. It works to treat other conditions by reducing swelling and redness and by changing the way the immune system works.