Perianal fistula
Perianal fistula is characterized by multiple chronic fistulous
tracts or ulcerating sinuses involving the perianal region. The cause is not
known, but apocrine gland inflammation (hidradenitis suppurativa), impaction
and infection of the anal sinuses and crypts, infection of the circumanal
glands and hair follicles, and anal sacculitis have all been proposed. The
gastrointestinal system becomes involved because of excessive scar tissue
formation around the anus. Self-mutilation can also be a major problem
associated with this disorder.
signalment
Dogs German shepherd dog and Irish setter most commonly affected breeds Mean age, 7 years (range, 7 months-12 years) No gender predisposition reported, but sexually intact dogs have a higher prevalence A genetic basis has been proposed, but not proven
signs
Vary with the severity and extent of involvement : Dyschezia, tenesmus, hematochezia, constipation, diarrhea, malodorous mucopurulent anal discharge, fecal incontinence, painful tail movements, licking and self-mutilation, anorexia, weight loss, reluctance to sit, posturing difficulties, and personality changes
causes and risk factors
Proposed causes involve an inflammatory component Low tail carriage and a broad tail base are risk factors predisposing the dog to inflammation and infection because of poor ventilation, accumulation of feces, moisture, and secretions High density of apocrine sweat glands in the cutaneous zone of the anal canal of German shepherd dogs Hidradenitis suppurativa may be associated with immune or endocrine dysfunction, genetic factors, and poor hygiene
diagnosis: differential diagnosis
Chronic anal sac abscess Perianal adenocarcinoma that is ulcerated and draining Rectal fistula
CBC/Biochemistry/Urinalysis
Results usually normal. Patients with inflammation may have an inflammatory leukogram.
other diagnostic procedures
Presumptive diagnosis is based on clinical signs and results of physical examination. Definitive diagnosis is made by biopsy of the affected area.
treatment
Surgery is considered the most effective treatment. However, a tremendous amount of controversy exists as to which surgical method should be used, and none of those currently employed result in consistent resolution of the problem. Surgical options include electrosurgery, cryosurgery, surgical debridement with fulguration by chemical cautery, exteriorization and fulguration by electrocautery, surgical resection, radical excision of the rectal ring, tail setting, tail amputation, and laser surgery. Each technique has advantages and disadvantages that must be weighed when making a choice. The primary objective of surgery is the complete removal or destruction of diseased tissue while preserving normal tissue and function. Multiple procedures may be necessary for complete resolution.
medications
Medical treatment of perianal fistulas is usually unrewarding and can be detrimental by delaying more definitive treatment and allowing progression. Medical palliation involves clipping hair from the affected area, daily antiseptic lavage, systemic and topical antibiotics, hydrotherapy, elevation of the tail, and systemic corticosteroids.
contraindications/possible interactions
Corticosteroids are contraindicated when infection is possible.
follow-up
After surgery for appropriate healing, signs of recurrence, and associated complications
Complications associated with the various surgical procedures include recurrence, failure to heal, dehiscence, tenesmus, fecal incontinence, anal stricture, and flatulence. The incidence of postoperative complications is directly related to severity of disease.
Prognosis is guarded for complete resolution except in mildly affected patients. Clients often become frustrated with the difficulty of attaining definitive resolution of this disorder.
references
Matthiesen DT, Marretta SM. Diseases of the anus and rectum. In: Slatter D, ed. Textbook of small animal surgery. 2nd ed. Philadelphia: WB Saunders, 1993;627-644. van Ee RT. Perianal fistulas. In: Bojrab MJ, ed. Disease mechanisms in small animal surgery. 2nd ed. Philadelphia: Lea & Febiger, 1993;285-286. Author James L. Cook
Consulting Editor Brent D. Jones
Current Recommendations for the Treatment of Perianal Fistula
Author Kyle Mathews, DVM, MS, DACVS
Introduction
The surgical treatment of perianal fistula has been fraught with complications and a high recurrence rate (generally, 40% to 50%). Recommended treatments have included cryosurgical destruction of diseased perianal tissues, electrofulguration, rectal pull-through, and caudectomy (tail amputation). Complications have included rectal stricture, recurrence, and fecal incontinence. Medical treatment with cyclosporine may be effective in some cases.
Discussion
The underlying cause of perianal fistula is not known. It is thought to be the extension of infection or inflammation of superficial tissues (hydradenitis) or of the anal sacs. Conformation has also been thought to play a role in the formation of a fistula, such as a tight tail base or a sunken or recessed anus. These anatomic peculiarities may result in a persistent fecal film in the perineal region, predisposing to infection. Reports of clinical response to immunosuppressive drugs suggest that perianal fistula may be a primary immune-mediated disease or have an immune-mediated component.
In one canine study, 9 of 27 (33%) German shepherd dogs with a fistula and histologically confirmed colitis had resolution of their fistula after being placed on a high dosage of corticosteroids and a hypoallergenic diet.1
An important change in the treatment of canine perianal disease occurred recently with the report that the immunosuppressive drug cyclosporine results in marked improvement or resolution of perianal fistula in many patients.2 After 16 weeks of treatment, the fistula healed in 17 of 20 dogs (85%). Humans with a form of chronic inflammatory bowel disease (Crohn's disease) may also develop perianal fistulation that often responds to cyclosporine.3
I typically start treatment of perianal fistula with administration of microemulsified cyclosporine (Neoral, Sandoz Pharmaceuticals, East Hanover, New Jersey) at 3 mg/kg PO q12h. Neoral comes in 50-ml vials (approximately $300 per vial) and the proper dose can be aspirated in a syringe and then added to an empty gelatin capsule. The drug is also available in 100-mg gelcaps, which is often close to the proper dose for the typical German shepherd with this disease.
I check the patient's trough plasma concentration of cyclosporine 2 weeks after beginning the medication and make appropriate dosage adjustments based on the results. The target concentration is 300 to 500 ng/ml (using an HPLC assay) or 500 to 750 ng/ml (using the TdX assay at North Carolina State University). Make sure you know which assay your laboratory is using. Most laboratories associated with human hospitals run this assay, but they may not for veterinary patients or it may be expensive.
Cyclosporine should be kept in a dark cupboard at room temperature. Blood samples should be drawn in the morning, 12 hours after the last evening dose was given, and before giving the dog his or her morning medications. The blood should be mailed in an EDTA (purple-topped) blood tube in a crush proof container to the laboratory by next-day delivery. Samples should not be sent on a Friday or before a holiday because they may not be delivered promptly. The sample does not have to be frozen for shipment.
The cyclosporine dosage is increased if the trough concentration is low, particularly if the response is minimal or absent after 1 month of drug administration. Trough concentrations as low as 75 ng/ml (HPLC) may be effective in some dogs.4
A decrease in fistula size is not usually seen for the first 2 weeks. However, many clients report an improvement in their dog's energy level, decreased licking at the area, and diminished tenesmus within the first 2 weeks.
Unanswered questions regarding cyclosporine and perianal fistulas include these:
What is the proper duration of treatment? I administer the drug to fistula patients for at least 2 weeks after complete resolution based on visual examination. It is unclear if these dogs should be treated longer in order to keep the disease in remission or if it is better to treat only during recurrent episodes. Small fistulas recurred in 7 of 17 dogs 2 to 24 weeks after discontinuing treatment.5 What is the underlying cause and reason that cyclosporine works? What is occurring at a cellular level before, during, and after treatment with cyclosporine?
Why do some dogs respond and others do not? One study showed no difference in the mean blood or intestinal tissue concentration of cyclosporine in human responders and non-responders with Crohn's disease.6
What ancillary treatments are appropriate (e.g., dietary modification and antibiotics)?
Should other medications be given to inhibit cyclosporine metabolism and thereby decrease the cost of treatment (e.g., ketoconazole)?
I currently recommend cyclosporine administration for the treatment of perianal fistula; however, medication costs and the surgical options and their potential complications need to be discussed so that the guardian can come to an informed decision. In addition, excision of persistent or recurrent fistulas may be required.
Summary
The cause of perianal fistula and why many dogs respond to treatment with cyclosporine is poorly understood. The cost of cyclosporine is prohibitive for some clients. However, the cost and risk of multiple potential surgeries must be considered as well. Cyclosporine has greatly simplified the treatment of perianal fistula in many animal patient. Questions regarding recurrence rate and long-term therapy will likely be answered within the next few years.
References
1. Harkin KR, Walshaw R, Reimann KA, et al. Association of perianal fistula and colitis in the German Shepherd Dog: response to high-dose prednisone and dietary therapy. J Am Anim Hosp Assoc 1996;32:515.
2. Mathews Karol A, Sukhiani HF. Randomized controlled trial of cyclosporine for treatment of perianal fistulas in dogs. J Am Vet Med Assoc 1997;211:1249.
3. Present DH, Lichtiger S. Efficacy of cyclosporine in treatment of fistula of Crohn's disease. Digest Dis Sci 1994;39:374.
4. Wooldridge JD, Gregory CR, Mathews KG, et al. Clinical evaluation of leflunomide alone, leflunomide and cyclosporine, and cyclosporine at varying dosages in the treatment of perianal fistulas in dogs. Submitted, J Am Vet Med Assoc, 1999.
5. Mathews KA, ibid.
6. Sandborn WJ, Tremaine WJ, Lawson GM. Clinical response does not correlate with intestinal or blood cyclosporine concentrations in patients with Crohn's disease treated with high-dose oral cyclosporine. Am J Gastroent 1996;91:37.
signalment
Dogs German shepherd dog and Irish setter most commonly affected breeds Mean age, 7 years (range, 7 months-12 years) No gender predisposition reported, but sexually intact dogs have a higher prevalence A genetic basis has been proposed, but not proven
signs
Vary with the severity and extent of involvement : Dyschezia, tenesmus, hematochezia, constipation, diarrhea, malodorous mucopurulent anal discharge, fecal incontinence, painful tail movements, licking and self-mutilation, anorexia, weight loss, reluctance to sit, posturing difficulties, and personality changes
causes and risk factors
Proposed causes involve an inflammatory component Low tail carriage and a broad tail base are risk factors predisposing the dog to inflammation and infection because of poor ventilation, accumulation of feces, moisture, and secretions High density of apocrine sweat glands in the cutaneous zone of the anal canal of German shepherd dogs Hidradenitis suppurativa may be associated with immune or endocrine dysfunction, genetic factors, and poor hygiene
diagnosis: differential diagnosis
Chronic anal sac abscess Perianal adenocarcinoma that is ulcerated and draining Rectal fistula
CBC/Biochemistry/Urinalysis
Results usually normal. Patients with inflammation may have an inflammatory leukogram.
other diagnostic procedures
Presumptive diagnosis is based on clinical signs and results of physical examination. Definitive diagnosis is made by biopsy of the affected area.
treatment
Surgery is considered the most effective treatment. However, a tremendous amount of controversy exists as to which surgical method should be used, and none of those currently employed result in consistent resolution of the problem. Surgical options include electrosurgery, cryosurgery, surgical debridement with fulguration by chemical cautery, exteriorization and fulguration by electrocautery, surgical resection, radical excision of the rectal ring, tail setting, tail amputation, and laser surgery. Each technique has advantages and disadvantages that must be weighed when making a choice. The primary objective of surgery is the complete removal or destruction of diseased tissue while preserving normal tissue and function. Multiple procedures may be necessary for complete resolution.
medications
Medical treatment of perianal fistulas is usually unrewarding and can be detrimental by delaying more definitive treatment and allowing progression. Medical palliation involves clipping hair from the affected area, daily antiseptic lavage, systemic and topical antibiotics, hydrotherapy, elevation of the tail, and systemic corticosteroids.
contraindications/possible interactions
Corticosteroids are contraindicated when infection is possible.
follow-up
After surgery for appropriate healing, signs of recurrence, and associated complications
Complications associated with the various surgical procedures include recurrence, failure to heal, dehiscence, tenesmus, fecal incontinence, anal stricture, and flatulence. The incidence of postoperative complications is directly related to severity of disease.
Prognosis is guarded for complete resolution except in mildly affected patients. Clients often become frustrated with the difficulty of attaining definitive resolution of this disorder.
references
Matthiesen DT, Marretta SM. Diseases of the anus and rectum. In: Slatter D, ed. Textbook of small animal surgery. 2nd ed. Philadelphia: WB Saunders, 1993;627-644. van Ee RT. Perianal fistulas. In: Bojrab MJ, ed. Disease mechanisms in small animal surgery. 2nd ed. Philadelphia: Lea & Febiger, 1993;285-286. Author James L. Cook
Consulting Editor Brent D. Jones
Current Recommendations for the Treatment of Perianal Fistula
Author Kyle Mathews, DVM, MS, DACVS
Introduction
The surgical treatment of perianal fistula has been fraught with complications and a high recurrence rate (generally, 40% to 50%). Recommended treatments have included cryosurgical destruction of diseased perianal tissues, electrofulguration, rectal pull-through, and caudectomy (tail amputation). Complications have included rectal stricture, recurrence, and fecal incontinence. Medical treatment with cyclosporine may be effective in some cases.
Discussion
The underlying cause of perianal fistula is not known. It is thought to be the extension of infection or inflammation of superficial tissues (hydradenitis) or of the anal sacs. Conformation has also been thought to play a role in the formation of a fistula, such as a tight tail base or a sunken or recessed anus. These anatomic peculiarities may result in a persistent fecal film in the perineal region, predisposing to infection. Reports of clinical response to immunosuppressive drugs suggest that perianal fistula may be a primary immune-mediated disease or have an immune-mediated component.
In one canine study, 9 of 27 (33%) German shepherd dogs with a fistula and histologically confirmed colitis had resolution of their fistula after being placed on a high dosage of corticosteroids and a hypoallergenic diet.1
An important change in the treatment of canine perianal disease occurred recently with the report that the immunosuppressive drug cyclosporine results in marked improvement or resolution of perianal fistula in many patients.2 After 16 weeks of treatment, the fistula healed in 17 of 20 dogs (85%). Humans with a form of chronic inflammatory bowel disease (Crohn's disease) may also develop perianal fistulation that often responds to cyclosporine.3
I typically start treatment of perianal fistula with administration of microemulsified cyclosporine (Neoral, Sandoz Pharmaceuticals, East Hanover, New Jersey) at 3 mg/kg PO q12h. Neoral comes in 50-ml vials (approximately $300 per vial) and the proper dose can be aspirated in a syringe and then added to an empty gelatin capsule. The drug is also available in 100-mg gelcaps, which is often close to the proper dose for the typical German shepherd with this disease.
I check the patient's trough plasma concentration of cyclosporine 2 weeks after beginning the medication and make appropriate dosage adjustments based on the results. The target concentration is 300 to 500 ng/ml (using an HPLC assay) or 500 to 750 ng/ml (using the TdX assay at North Carolina State University). Make sure you know which assay your laboratory is using. Most laboratories associated with human hospitals run this assay, but they may not for veterinary patients or it may be expensive.
Cyclosporine should be kept in a dark cupboard at room temperature. Blood samples should be drawn in the morning, 12 hours after the last evening dose was given, and before giving the dog his or her morning medications. The blood should be mailed in an EDTA (purple-topped) blood tube in a crush proof container to the laboratory by next-day delivery. Samples should not be sent on a Friday or before a holiday because they may not be delivered promptly. The sample does not have to be frozen for shipment.
The cyclosporine dosage is increased if the trough concentration is low, particularly if the response is minimal or absent after 1 month of drug administration. Trough concentrations as low as 75 ng/ml (HPLC) may be effective in some dogs.4
A decrease in fistula size is not usually seen for the first 2 weeks. However, many clients report an improvement in their dog's energy level, decreased licking at the area, and diminished tenesmus within the first 2 weeks.
Unanswered questions regarding cyclosporine and perianal fistulas include these:
What is the proper duration of treatment? I administer the drug to fistula patients for at least 2 weeks after complete resolution based on visual examination. It is unclear if these dogs should be treated longer in order to keep the disease in remission or if it is better to treat only during recurrent episodes. Small fistulas recurred in 7 of 17 dogs 2 to 24 weeks after discontinuing treatment.5 What is the underlying cause and reason that cyclosporine works? What is occurring at a cellular level before, during, and after treatment with cyclosporine?
Why do some dogs respond and others do not? One study showed no difference in the mean blood or intestinal tissue concentration of cyclosporine in human responders and non-responders with Crohn's disease.6
What ancillary treatments are appropriate (e.g., dietary modification and antibiotics)?
Should other medications be given to inhibit cyclosporine metabolism and thereby decrease the cost of treatment (e.g., ketoconazole)?
I currently recommend cyclosporine administration for the treatment of perianal fistula; however, medication costs and the surgical options and their potential complications need to be discussed so that the guardian can come to an informed decision. In addition, excision of persistent or recurrent fistulas may be required.
Summary
The cause of perianal fistula and why many dogs respond to treatment with cyclosporine is poorly understood. The cost of cyclosporine is prohibitive for some clients. However, the cost and risk of multiple potential surgeries must be considered as well. Cyclosporine has greatly simplified the treatment of perianal fistula in many animal patient. Questions regarding recurrence rate and long-term therapy will likely be answered within the next few years.
References
1. Harkin KR, Walshaw R, Reimann KA, et al. Association of perianal fistula and colitis in the German Shepherd Dog: response to high-dose prednisone and dietary therapy. J Am Anim Hosp Assoc 1996;32:515.
2. Mathews Karol A, Sukhiani HF. Randomized controlled trial of cyclosporine for treatment of perianal fistulas in dogs. J Am Vet Med Assoc 1997;211:1249.
3. Present DH, Lichtiger S. Efficacy of cyclosporine in treatment of fistula of Crohn's disease. Digest Dis Sci 1994;39:374.
4. Wooldridge JD, Gregory CR, Mathews KG, et al. Clinical evaluation of leflunomide alone, leflunomide and cyclosporine, and cyclosporine at varying dosages in the treatment of perianal fistulas in dogs. Submitted, J Am Vet Med Assoc, 1999.
5. Mathews KA, ibid.
6. Sandborn WJ, Tremaine WJ, Lawson GM. Clinical response does not correlate with intestinal or blood cyclosporine concentrations in patients with Crohn's disease treated with high-dose oral cyclosporine. Am J Gastroent 1996;91:37.
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