Yuku free message boards

Introduction

Perianal fistulas is a chronic, debilitating disease. German Shepherds represent approximately 84% of the total cases of perianal fistulas. The second most common breed is the Irish Setter. Other reported breeds include Labrador Retrievers, Old English Sheepdogs, Border Collies, Bulldogs, and various mix breeds. The middle aged intact male dog is typically affected. The mean age being 5-7 years. Common clinical signs include: tenesmus, dyschezia, self mutilation , malodorous, mucopurulent discharge, low tail carriage, perianal licking, weight loss, and lethargy. However, this is a gradual and progressive disease and clinical signs can go unnoticed. The gross lesions are often missed by the owners due to the long hair surrounding this region.

To properly examine the perianal area, sedation is often required. Clipping and gently cleansing should be performed to visually assess the degree of involvement. Lesions can vary in appearance from superficial pinpoint fistulas to extensive large ulcerated areas extending deep into the rectal tissues. The tail head may be involved in some cases. A rectal exam should be performed and may reveal thickening and fibrosis of the anus and rectum. Anal tone as well as stricture presence should be evaluated. The anal sacs should be palpated and expressed for possibility of involvement. Other rule outs to consider are chronic anal sac abscessation with rupture, trauma, and perianal neoplasia.

Etiology

The etiology of perianal fistulas remain unclear. It has traditionally been suggested that there is an anatomic predisposition for the formation of perianal fistulas. The broad based tail of the German Shepherd Dog and the low tail carriage of the Irish Setter as well as high density of apocrine sweat glands were thought to cause an environment poor in ventilation and allow moisture and bacteria from feces, rectal mucus, or anal sac secretion to accumulate leading to inflammation. However, breeds with similar anatomy such as the Belgian Tervurn and Gordon Setter do not seem predisposed to development of perianal fistulas. An immunologic defect is highly suspected. There is a reported link between colitis in the German Shepherd Dog and perianal fistulas similar to the development of perianal fistulas in people with Crohn's Disease. The response to immunosuppressive medications is encouraging.

Treatment

Treatment of perianal fistulas is a frustrating process. Traditional medical therapy consisting of antibiotics and local hygiene are only considered palliative at best. Neutering is recommended as intact males seem to be more involved.

Surgical Treatment

Various surgical procedures have been described to help control perianal fistulas. Surgical excision anal sacculectomy is preferred by some surgeons. The goal with this procedure is to remove all diseased tissue. However, results are quite variable. In two studies; recurrence rates were high (45 and 56%) while in two other studies recurrence rates were more reasonable (13 and 17%). Stenosis is a potential complication as well as fecal incontinence; 29% reported in one study.² Cryotherapy is also a technique described. The diseased tissue is destroyed through application of extreme cold. Cryonecrosis of the fistulous tracts occurs and is followed by sloughing of the diseased tissue and healing via second intention. There is an advantage of analgesia however the odor and appearance of the sloughed tissue can be quite objectionable to owners. A second procedure is common (50%) due to the deep scarring and anal stenosis that may be occur with cryotherapy. Deroofing and Fulguration is an additional technique described. This procedure only causes destruction of the superficial tissue layers. Therefore, there is less risk of causing fecal incontinence; however, this procedure is relatively ineffective in severe cases. Tail amputation has also been described. The theory behind this procedure being to change the local environment in hopes to break the cycle that perpetuates the disease. There is a reported 80% success rate and 20% recurrence rate. Fecal incontinence and stenosis are relatively uncommon. This procedure may be combined with deroofing and fulguration and may lead to better ventilation and drying. However, the deeper fistulas will not resolve. Laser excision using a frosted, sapphire tip and continuous impulse of 13-15 watts have been reported to use to excise perianal fistulas. However, fecal tone was reduced and flatulence increased in 60% of cases and fecal incontinence occurred in 20%; but the incontinence was able to be controlled with dietary management. The overall success rate of laser excision was 95%; particularly in relieving pain in patients with anal stenosis.

Medical Treatment

Recent treatment recommendations have concentrated on the immune cascade associated the disease process. Cyclosporine has been advocated in recent reports. Cyclosporine is a potent immunosuppressive drug without myelosuppression or cytotoxicity. Cyclosporine blocks production and responsiveness to IL2, IL6, and IFN by CD4 lymphocytes. German Shepherds are predisposed to other immune mediated disease such as inflammatory bowel disease and small intestinal bacterial overgrowth in which there is a loss of balance between pro-inflammatory and anti-inflammatory stimuli. Humans with Crohn's disease with coinciding perianal fistulas also have disruption of normal T cell regulation in which treatment with cyclosporine has been successful.

In 1997, Dr. Matthews et al performed a study in which 20 German Shepherd Dogs with perianal fistulas were treated with cyclosporine or were in a placebo group dosage. At 4 weeks, all dosage dogs being treated with cyclosporine were improved (decreased surface area of the fistulas, lessened tenesmus, decreased licking and chewing of the perianal region) and 70% of the placebo group had worsened. At 16 weeks, 85% of cyclosporine treated dogs were completed healed. However, fistulas did recur in 41% and additional cyclosporine treatment was necessary or surgical excision was pursued. However, in the dogs that required surgery, the lesions were significantly less extensive than if they had not been treated; therefore, lessening the risk of incontinence from surgical trauma.

A downside to cyclosporine is that is relatively expensive and is rapidly metabolized in the dog; 2.8 times faster than in humans. Therefore, it would be advantageous to develop a drug regimen that would reduce the amount of cyclosporine necessary to achieve desired whole blood concentrations. Ketoconazole has been shown to decrease clearance of cyclosporine via inhibition of hepatic P450IIIA microsomal enzymes. Previous experimental studies have demonstrated ketoconazole administration can double cyclosporine half life, increase stable blood concentrations, and reduce cyclosporine metabolites. The maximum ketoconazole dose is 10 mg/kg but effects are observed at 2.5 mg/kg. Ketoconazole may also be beneficial due to its activity against various bacteria, fungal, and yeast species.

In one study with dogs being treated with both cyclosporine and ketoconazole, 66% underwent complete remission and all but one of the remaining dogs had significant reduction of size of fistulas. Five of the 8 dogs that achieved remission had recurrence. Dogs that had recurrence had a longer duration of disease process prior to treatment. (166 weeks vs 15 weeks) Cyclosporine and ketoconazole were again initiated and all dogs had resolution of clinical signs. In cost analysis, the combination of cyclosporine and ketoconazole had between 36-71% savings versus single agent cyclosporine therapy.

There is a new cyclosporine formulation, Neoral that is microemulsified resulting in more consistent blood levels. The starting dose is 5-10mg/kg divided BID. Blood levels should be measured 48 hours after initiation and then periodically using a monoclonal RIA only due to other assays' ability to cross react with cyclosporine metabolites which may falsely indicate higher blood concentrations. Adverse reactions of cyclosporine include vomiting, hair loss, and opportunistic fungal or bacterial infections.

Tacrolimus has a mechanism of action similar to cyclosporine ; however it is 10-100 times more potent and has less side effects. It also has the advantage of being topically applied therefore higher local levels can be achieved without causing systemic side effects. In a study by Missengher, 50% of dogs had complete resolution after 16 weeks. Once a day application is best with no improvement seen with additional dosing. There is also a cost advantage with Tacrolimus. The average cost is $53/month vs $376/month with cyclosporine. Tacrolimus is becoming more available in the United States.

For those owners with significant financial constraints, there has been some response seen with high dose prednisone and novel protein diets. In a study of 27 German Shepherd Dogs, 1/3 responded completely, 1/3 showed partial improvement, and 1/3 had no response to therapy.