What Is Anal Furunculosis

What is perianal fistula?
Perianal fistula is a painful, chronic condition in which single or multiple ulcerated tracts develop in the tissue around the anus. No one clear cause has been established, although many have been considered. Some of the factors involved appear to be a broad tail base and low tail carriage, and an increased density of sweat glands in the anal region. It is these sweat glands that become inflamed and infected, leading to the draining sinus tracts typical of this condition.

How is perianal fistula inherited?
unknown, but there is a strong breed predisposition for the breeds mentioned below.

What breeds are affected by perianal fistula?
German shephard , Irish setter

For many breeds and many disorders, the studies to determine the mode of inheritance or the frequency in the breed have not been carried out, or are inconclusive. We have listed breeds for which there is a consensus among those investigating in this field and among veterinary practitioners, that the condition is significant in this breed.

What does perianal fistula mean to your dog & you?
This condition is painful for your dog. The types of signs you will see include straining or pain with defecation, bleeding, constipation, fecal incontinence, licking of the area, and malodorous anorectal discharge. These signs worsen as more tissue in the area around the anus becomes affected.

How is perianal fistula diagnosed?
Diagnosis is usually straightforward, based on your description of what you observe in your dog, and on physical examination in which your veterinarian will find single or multiple areas of ulceration and draining tracts, with pus and blood. Your veterinarian may also take a skin biopsy if s/he suspects a tumour in the area (which usually has a more raised appearance, but can also be associated with extensive ulceration).

How is perianal fistula treated?
This is a difficult condition to treat. Medical treatment (combination of antibiotics, antiseptics, and anti-inflammatory drugs) only provides temporary relief, and is usually not successful in clearing up the condition. Generally surgery is required, and there are several methods used including surgical removal of the tracts, freezing or cautery of the tissue, and tail amputation. Possible post-operative complications include significant bleeding, fecal incontinence, and recurrence of the tracts.

In mild cases, surgery often results in complete resolution of the problem, without recurrence. Where the problem is more severe (more tissue destruction), there is a lower rate of success and a higher occurrence of complications. Your veterinarian will discuss all this with you when considering what is best for your dog.

Breeding advice
Although the inheritance (or even the cause of the condition) is not understood, it is preferable not to breed affected animals.

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Managing Anal Furunculosis in Dogs

presented by Dr Mandy Burrows
Dermclub 1, 2006:

INTRODUCTION
• Canine anal furunculosis (perianal fistula) is a chronic, painful, progressive inflammatory and ulcerative disease associated with the perianal, anal, and/or perirectal tissues.

• The disease is characterized by the presence of focal or multifocal, dissecting ulcerative sinus tracts of varying diameter, depth, and connectivity developing in the perianal tissue which can extend 360° circumferentially around the anus.

• Canine anal furunculosis has a clinical appearance similar to that of perianal fistula in humans, which is often associated with granulomatous enteritis (Crohn’s disease).

SIGNALMENT AND CLINICAL SIGNS
• German shepherds with this disease appear to be overrepresented, with one report showing that 84% of affected dogs were German shepherds. Other breeds reported include Irish setters, Collies, Border collies, Old English sheepdogs, Labrador retrievers, English bulldogs, Beagles, Bouvier des Flandres, Spaniels, and mixed breeds.

• The disease usually affects middle-aged dogs with a mean age of 4 to 7 years with no sex predilection.

• Clinical signs associated with anal furunculosis are listed below.

PATHOGENESIS
• A definitive cause of anal furunculosis has not been described; however, many theories have been proposed.

• The older hypotheses include poor conformation of the perianal region and tail (broad-based low tail carriage), anal crypt faecalith impaction resulting in abscessation, spread of infection from the anal glands or anal sacs, trauma, and foreign body reaction. Unfortunately, little evidence supports any of these hypotheses.

• The current theory involves a multifactorial immune-mediated disease process.
An immune-mediated process is suspected because both canine anal furunculosis and Crohn’s disease respond to immunomodulation.

Accumulating evidence shows that Crohn’s disease is the result of an unbalanced host immune response to intestinal triggers in genetically susceptible humans. Because German Shepherds with canine anal furunculosis also have clinical and histologic evidence of colitis (inflammatory bowel disease [IBD]), it is possible that enteral triggers (dietary antigens, bacterial antigens, superantigens) are initiators of canine anal furunculosis as well.

PHYSICAL EXAMINATION
• Examination of the perianal area of patients with anal furunculosis usually requires sedation or general anaesthesia because of severe pain.

• Clipping the perianal region is often necessary to assess the severity of disease. Lesions may vary from superficial pinpoint tracts to large ulcerated areas. Several of these tracts may often be interconnected. Tracts may tunnel deep within the surrounding tissue and occasionally communicate with the rectum, anus, and/or anal sacs. 

• The tracts should be probed with a sterile, blunt instrument to determine their extent and involvement with regional structures.

• A rectal examination should be performed to assess the external anal sphincter, anal sacs, and rectal mucosa. Thickening (i.e., fibrosis) of the anus and rectum can be palpated during the rectal examination. It is important to determine whether there is evidence of anorectal stenosis and/or perineal hernia, which would affect the prognosis. The anal sacs may be normal,
impacted, or ruptured. In addition, the anal sacs may be incorporated within surrounding tissue fibrosis.

• Cannulation of the anal sac ducts determines whether they are occluded. Flushing the anal sacs with sterile saline may reveal a previously unobserved fistulating tract.

• The primary differential diagnoses include anal sac abscessation, perianal adenoma, anal sac adenocarcinoma, anal squamous cell carcinoma, rectal neoplasia, atypical bacterial infection, mycosis, and oomycosis (pythiosis, lagenidiosis).

DIAGNOSTIC EVALUATION
• The diagnosis of canine anal furunculosis is based on history, physical examination findings, and ruling out other primary diagnostic differentials.

• Superficial cytology is a standard tool for evaluating the cutaneous and sinus tract microenvironment. It invariably reveals pyogranulomatous inflammation with a mixed bacterial population.

• Fine-needle aspiration of an enlarged anal sac is warranted to rule out abscessation or neoplasia.

• Sinus tracts should be cultured with a sterile swab or tissue biopsy for bacterial culture and susceptibility testing because controlling secondary infection with antibiotics may take weeks to months.

• Tissue biopsy for histopathology can be used to verify the tentative diagnosis of canine anal furunculosis and to rule out neoplasia. Biopsy sites often have to heal by second intention.

• Other diagnostics that may prove useful include colonoscopy with biopsy, and pelvic radiography.

MANAGEMENT
SURGICAL
• Primary surgical treatment of canine anal furunculosis was previously advocated. Surgical procedures involved either destroying the epithelial lining of sinus tracts or total en bloc tract excision to remove diseased tissue and prevent recurrence.

• Surgical treatment included surgical excision, chemical cauterization, cryotherapy, deroofing and fulguration, and laser (i.e., neodymium: yttrium aluminum garnet) excision. Tail amputation was also recommended as a means of reducing faecal soiling and contamination over the perianal area.

• These procedures reportedly had varying success rates (48% to 97% of cases) but a high rate of recurrence of disease (approximately 70%), with some surgical techniques necessitating further surgical treatments.

• Other frequent serious complications such as anal stenosis (up to 15% of cases, with the incidence approaching 47% following cryotherapy) and faecal incontinence (in up to 29% of cases) were reported.

MEDICAL
• Fortunately, medical management in recent years has shed new light on this devastating disease. Several studies have reported favourable results with immunosuppressive or immunomodulating drug regimens, including cyclosporin, tacrolimus, and azathioprine and metronidazole. Conventional immunosuppression with glucocorticoids has also been reported, albeit without
the same level of success.

• Consequently, clinicians can now give their clients new therapeutic options that can positively affect the prognosis. It is paramount for clinicians to discuss with clients the goal, effectiveness, length, and cost of therapy before implementing it.

• It is important for owners to understand that canine anal furunculosis is a chronic relapsing and remitting disease that can be managed but not necessarily cured. Lifelong therapy may be required as with other immunemediated diseases. If one drug combination does not achieve the defined goal, another drug protocol is warranted.

• The first goal of therapy should be to alleviate large bowel clinical signs such as tenesmus, dyschezia, hematochezia, constipation or obstipation, diarrhea, ribbon-like stool, increased frequency of defecation, and perianal pain. The second goal of therapy should be to reduce the diameter, depth, extent, and recurrence of sinus tracts.

• Medical management comprises immunosuppressive or immunomodulatory treatment as well as hygiene, and antimicrobial therapy.

• As with treating other immune-mediated diseases, immunosuppressive therapy consists of induction and maintenance phases. The induction phase usually consists of oral systemic therapy to alleviate clinical signs associated with pain and inflammation. This phase can last 8 to 20 weeks.

• Once signs of pain and lesional skin have improved, maintenance therapy should be initiated. It may consist of the lowest effective dose of oral therapy administered during induction and/or topical therapy. Clinicians should not prescribe topical therapy until owners can apply it safely and without discomfort to their dogs.

GLUCOCORTICOIDS, AZATHIOPRINE AND METRONIZADOLE

• We have used glucocorticoids with reasonable success but usually combined with either azathioprine or metronidazole. This therapy is not cost prohibitive for most clients.

• Prednisolone should be initiated at immunosuppressive dose (2 to 4 mg/kg PO q24h or divided q12h), usually for 3 to 6 weeks to reduce pain, inflammation, and the extent of sinus tract involvement. Once the therapeutic goal has been achieved, the glucocorticoid dose should be slowly tapered over weeks to months to the lowest effective oral, every-other-day dose (ideally prednisone ≤1 mg/kg).

• Azathioprine suppresses both humoral and cell-mediated immunity and the potential side effects include gastrointestinal (GI) upset, bone marrow suppression, hepatotoxicity, and pancreatitis. When used as an adjuvant to glucocorticoids, azathioprine can be administered at 1.5 to 2.0 mg/kg/day PO for the first 2 to 4 weeks and then every other day.

• Metronidazole has immunomodulating effects, is effective at reducing faecal bacterial colonization of the perianal area, and is an antiprotozoal. Its potential side effects include anorexia, GI upset, central nervous system toxicity, and hepatotoxicity. We occasionally administer metronidazole (10 to 15 mg/kg PO q12h) in combination with glucocorticoids.

CYCLOSPORIN (CSA)
• CsA appears to be the most effective medical treatment to date for canine anal furunculosis. Table 1 summarizes the results of all the published trials utilising either CsA alone or in combination with ketoconazole.

• The most effective therapeutic dosing regimen has not yet been clearly established. In most studies, CsA was given twice daily but data from recent studies suggest that once daily administration is as beneficial as twice daily dosing.

• Lesion resolution appears to be more rapid with the higher dosages, but clinical signs also improved with dosages ranging from as low as 2 to 5 mg kg 1. Short protocols with high dosages resulted in fast remission and high recovery rates, but they were likely to be followed by relapses of clinical signs after the discontinuation of treatment. Longer treatment protocols (> 13 weeks) decrease the rate of relapse.

GIVING KETOCONAZOLE WITH CYCLOSPORIN
• Coadministration of ketoconazole with CsA has been advocated to reduce the daily CsA dose and hence cost to clients. Ketoconazole inhibits CsAmetabolizing enzymes (i.e., cytochrome P-450 system), thereby decreasing CsA clearance while increasing CsA blood concentration.

• The level of metabolizing enzyme inhibition is quite variable among individuals. Therefore, the resulting CsA blood concentration is variable and cannot be predicted. It should also be remembered that ketoconazole has its own adverse side effects and drug interactions that might prohibit its use.

• The co-administration of ketoconazole decreases the dose of CsA needed to induce remission. A dosage of 1 mg kg 1 of CsA combined with 10 mg kg 1 of ketoconazole for 16 weeks was found to be effective in one study (Mouatt et al 2002) and is currently the protocol we use in the dermatology clinic.

• Other clinicians prefer to use a higher induction dose of 5 mg kg 1 CsA in combination with 5 mg kg 1 of ketoconazole for a shorter induction period of 6 to 12 weeks before tapering the CsA dose (beginning with a reduced daily dose is typical). If adverse effects are noted during ketoconazole administration, CsA trough blood levels should be determined by highpressure
liquid chromatography to rule out potential CsA cytotoxicosis. Also, ketoconazole administration should be discontinued and the cyclosporin dose either reduced or discontinued pending CsA blood level results.

• Once clinical signs have substantially resolved, either the dose of CsA can be reduced by 20% to 40% and given daily or the same dose can be administered every other day. Continued dose tapering should be based on clinical response and lack of relapse. Tapering CsA too quickly is a frequent cause of clinical relapse.

MEASURING CYCLOSPORIN TROUGH LEVELS
• A direct relationship between CsA blood trough concentration and clinical efficacy in treating canine anal furunculosis has not been definitively proven and we do not routinely measure CsA trough blood levels. This tool should be reserved for select patients, such as those receiving concurrent ketoconazole, those not improving as expected, and those in which drug toxicosis is
suspected. When trough levels are needed, the high-pressure liquid chromatography method is recommended. Unfortunately, this method is available in only select laboratories and is expensive.

Table 1. Results of CsA Therapy for Canine Anal Furunculosis

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Immunosuppressive or Immunomodulatory Therapy: Maintenance

TACROLIMUS
• Tacrolimus has pharmacologic actions very similar to those of CsA but is 10 to 100 times more potent. It is applied topically to dogs because systemic administration requires careful drug monitoring. All studies thus far indicate that significant levels of tacrolimus do not accumulate in the blood when it is given topically. The drug is currently used as a topical immunomodulator in children and adults with atopic eczema. The most common side effects in humans are stinging and burning.

• Topical tacrolimus (Protopic 0.1% ointment, Fujisawa Health Care) has been reported to completely heal sinus tracts in 50% of dogs or markedly improve lesions in 90% of dogs when applied once or twice daily to treat anal furunculosis. In this study, the severity of canine anal furunculosis was graded as mild to moderate before therapy. In dogs that healed completely with several months of remission, tacrolimus was applied up to 16 weeks. No major complications were reported in any of the dogs (Misseghers 2000).

• If clinical signs of canine anal furunculosis are relatively mild at initial presentation and the dog does not object to topical therapy, tacrolimus may be administered alone. Tacrolimus is not approved for use in dogs. 

• As induction therapy is tapered, topical tacrolimus can be applied to the perianal region twice daily using a gloved hand. Induction therapy tends to be greatly reduced with concurrent tacrolimus therapy. We continue topical tacrolimus indefinitely regardless of whether induction therapy can be completely discontinued. Application of tacrolimus should be reduced to the lowest frequency that controls inflammation (usually every 24 to 72 hours). If tacrolimus is not used, the lowest possible dose of induction therapy should be given every 24 to 72 hours, depending on the drug(s) used.

Hygiene Therapy
• Antibiotic therapy is recommended to control secondary infection and antibiotic selection should be based on bacterial culture and susceptibility results. Empiric therapy with either amoxicillin–clavulanic acid or metronidazole is useful, pending culture results. Once the patient tolerates topical therapy, mupirocin ointment (Bactroban, Pfizer) applied once or twice daily may help reduce bacterial colonization.

• It is important to keep the perianal region clean and dry. Clipping and cleaning the perianal region under sedation can assist. Baby powder lightly applied to the surrounding perineum may reduce regional relative humidity. At home, antimicrobial shampoo therapy may be helpful once the patient will tolerate it.

MONITORING
• Reexaminations are usually scheduled every 6 weeks. Tracking the degree of improvement in clinical signs since the initial visit is important at each reexamination.

• Signs include tenesmus, dyschezia, hematochezia, constipation or obstipation, diarrhoea, ribbon-like stool, increased frequency of defecation, perianal licking, self-mutilation, perianal pain, scooting, offensive odour, low tail carriage, and weight loss. Although there may be several small sinus tracts, the owner may be satisfactorily impressed if signs of pain are reduced. Cutaneous reepithelialization may occasionally supersede the filling of sinus tracts, resulting in epithelialized tunnels, which were not associated with clinical problems in one study (Mouatt 2002)

• One of the most useful tools for monitoring improvement in canine anal furunculosis is a rectal examination while the patient is not sedated. Patients become less hesitant and require less restraint during rectal examinations as their clinical signs, specifically pain, improve. However, sedation is often needed during the first few reexaminations. The perianal, anal, and rectal tissues should be assessed. The anal sacs should be palpated and expressed if needed. The degree of tissue thickening (i.e., fibrosis) should be assessed during the rectal examination. In general, tissue thickening gradually reduces with time in patients that respond to treatment. Perianal cytology can be used to determine whether antibacterial treatments are still indicated.

ADJUNCTIVE TREATMENT
• Unfortunately, all dogs with anal furunculosis do not completely respond to medical management alone. Adjunctive surgical therapy is warranted if affected tissue hinders improvement in pain and/or healing or inflammation continues to expand despite aggressive medical treatment. Despite differences among surgical techniques previously described, the goal of surgical treatment is to remove or destroy diseased tissue. This may include anal sacculectomy. As previously noted, it appears that surgical outcomes improve with prior medical treatment.

• The carbon dioxide laser has been an effective adjunctive tool in treating canine anal furunculosis in some dermatology practices in the US. Lasers are used to ablate and/or excise ulcerative necrotic tissue in patients with canine anal furunculosis.

FUTURE TREATMENTS
• To achieve and maintain remission in humans with Crohn’s disease, several new and emerging therapeutic options are being used. Many of these agents are designed to precisely block or enhance immunologic events (i.e., cell signalling, leukocyte adhesion) believed to be involved in the pathogenesis of Crohn’s disease. Specifically, monoclonal anti–TNF-a antibodies (i.e., infliximab, cytidine diphosphate-571), soluble TNF-a receptor antagonists (i.e., etanercept), recombinant IL-10 (i.e., antiinflammatory cytokine), and intercellular adhesion molecule antagonists (i.e., natalizumab, alicaforsen) have been used with varying success in patients with Crohn’s disease.

• In addition to these treatments, use of probiotics (i.e., products containing microorganisms that beneficially alter the compartmental microflora of a host; e.g., Lactobacillus spp) in patients with Crohn’s disease is showing encouraging results.

• Perhaps once the veterinary community elucidates the immunopathogenesis of canine anal furunculosis, similar specific immune-altering therapies may prove useful in managing the disease.

REFERENCES
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Day MJ, Weaver BM: Pathology of surgically resected tissue from 305 cases of anal furunculosis in the dog. J Small Anim Pract 33:583–589, 1992.
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Ellison GW: Treatment of perianal fistulas in dogs. JAVMA 206(11):1680–1682, 1995.
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Elkins AD, Hobson HP: Management of perianal fistulae: A retrospective study of 23 cases. Vet Surg 11:110–114, 1982.
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Description
Anal furunculosis (or perianal fistulas) are deep unsightly sinuses that track through the skin, sometimes with flat open areas of ulceration. They are usually confined to the skin around the anus, but in severe cases they can spread as far as the flanks and run down the inside of the hindlegs. Technically they are NOT fistulas because they course only within the skin and do not open into another organ. Although they are near the anal sacs (scent glands) the sinuses do not connect with them, nor do they connect with the rectum or colon.

Cause
The cause of anal furunculosis is unknown.

The sinuses are not caused by infection, although secondary bacterial infection may be present. Some authors have suggested that dogs that carry the tail tightly against the anal region may be predisposed to develop furunculosis due to poor ventilation but this has not been proved. Others have suggested that there may be impaction of the local crypts of Morgagni.

When the sinuses are tracked back to their source they do not reach the anal sacs (scent glands) or the rectum or colon, as was suggested by some authors who were comparing the disorder with Crohne's Disease in humans..

Breed Occurrence
The disease occurs almost exclusively in the German Shepherd Dog. It is seen in both sexes and in German Shepherd crosses as well. It usually initially occurs in dogs aged 3-8 years.

Signs
The skin lesions are irritable resulting in self-trauma, and affected dogs often  lick and bite at the affected region. There may be pain, difficulty (or reluctance) and straining during defaecation. If the lesions spread down the legs the dog may walk with a straddled gait. Affected dogs are often tail-shy and won't allow people near their rear end, or to touch or lift their tail.

Complications
Repeated recurrences are common, and repeated surgery or cryosurgery can lead to fibrosis making defaecation difficult. Affected patients are often very tail-shy and reluctant to allow inspection of the area , or touching/lifting of the tail

Diagnosis
The diagnosis is confirmed at physical examination and by ruling out other causes for the lesions

Treatment
Treatment with drugs alone has generally not been successful, although recent reports suggest that cyclosporin may be efficacious

There are two main forms of surgical treatment :
Radical surgery where all the diseased tissue is removed surgically (excised and debrided) and the wounds are left open to heal by second intention. If the debrided skin is sutured it will often breakdown.
Cryosurgery - applying freezing liquid nitrogen, or by applying an ice-ball on a cryoprobe to the diseased tissue.  

Because of the extent of the lesions these treatments often have to be repeated several times.

Prognosis
The prognosis is guarded as recurrence is common
Long term problems