standards of CARe PERIANAL FISTULA APRIL 2009 DIAGNOSTIC CRITERIA Peer Reviewed

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1 Peer Reviewed CE APRIL 2009 standards of CARe EMERGENCY AND CRITICAL CARE MEDICINE VOL CE CONTACT HOURS FROM THE PUBLISHER OF COMPENDIUM PERIANAL FISTULA Matt S. Takara, DVM, MSpVM Major, Veterinary Corps United States Army Fort Bragg, North Carolina Sally Bissett, BVSc, MVSc, DACVIM Assistant Professor, Internal Medicine Department of Clinical Sciences North Carolina State University Raleigh, North Carolina Canine perianal fistula (anal furunculosis) is a chronic, painful, progressive, and potentially debilitating inflammatory condition involving the perianal, anal, and perirectal tissue of dogs. Clinical signs are associated with inflammation and irritation of the affected tissue. early in the course of the disease, only erythema and pinpoint draining tracts may be noted. these lesions often progress to large, chronic, ulcerated sinus tracts that can affect the entire perianal region. Perianal fistulas seen with Crohn s disease in humans (fistulating Crohn s disease) are believed to be immune-mediated in origin, although perianal sepsis also plays a role. Antimicrobial therapy with metronidazole or ciprofloxacin; immunosuppression with azathioprine, mercaptopurine, cyclosporine, or tacrolimus; antitumor necrosis factor therapy; and surgery are all established treatments for this condition in humans. the several clinical similarities between the canine and human forms of this disease have led to increased use of immunomodulating therapies for canine perianal furunculosis. DIAGNOSTIC CRITERIA Historical Information Gender Predisposition some studies report that male dogs are more commonly affected than females. the severity of tissue inflammation and clinical signs may be worse in intact female dogs during estrus. Age Predisposition the mean age of affected dogs is 5 6 years. the age range of affected dogs is 1 12 years. Breed Predisposition the German shepherd is the most commonly affected breed (>80% of reported cases). German shepherds have an increased density of apocrine sweat glands in the zona cutanea, which may be an associated risk factor. Other breeds that have been reported include Irish setter, Labrador retriever, Old english sheepdog, collie breeds, spaniel breeds, and Bouvier des Flandres. Owner Observations Persistent licking of the perianal region is the most common presenting complaint. Hematochezia, dyschezia, or tenesmus. Constipation. Fecal incontinence. Chronic, bloody to mucopurulent, malodorous perianal discharge. Abnormal tail carriage or tail chasing. Anorexia and lethargy. Weight loss. Behavioral changes. Also in this issue: 5 spontaneous Pneumothorax In partnership with the Veterinary Emergency and Critical Care Society Visit SOCNewsletter. com VECCS. org

2 Other Historical Considerations/Predispositions A broad-based tail, with or without low tail carriage, is believed to be associated with perianal fistulas. Physical Examination Findings Most affected dogs are normal in appearance. When the tail is elevated for examination, variable amounts of pain may be elicited, depending on the severity of lesions and the dog s tolerance, so a thorough examination of the perianal region may be difficult or impossible without heavy sedation or anesthesia. Visual examination reveals single or multiple ulcerated draining tracts. the fistulas may be difficult to see if they are small or lack overt cutaneous ulcerations. smaller lesions may become more evident as the lesions coalesce or begin to ulcerate. digital rectal examination is essential to: determine the depth of the lesions and the extent of fibrotic changes. detect rectal strictures and abnormal anal tone. evaluate the anal sacs, which may be secondarily involved. Laboratory Findings Minimum database (biochemistry panel, complete blood count, and urinalysis) findings are often nonspecific or not significantly abnormal. Bacterial cultures performed on deep tissue samples often reveal Escherichia coli, Staphylococcus aureus, β-hemolytic Streptococcus spp, and Proteus mirabilis. Bacterial infection of deeper tissue is believed to occur after cutaneous ulceration. Other Diagnostic Findings Approximately 50% of dogs with perianal fistulas have histopathologic evidence of colitis. Summary of Diagnostic Criteria the diagnosis of perianal fistulas can be based on the clinical signs and physical examination findings. Diagnostic Differentials Anal sac abscessation with secondary fistulas can be ruled out by rectal examination of anal sacs and absence of other fistulous tracts that are not associated with the anal sacs. A B O U T V E C C S the Veterinary emergency and Critical Care society was formed in 1978 in an effort to raise the level of patient care for seriously ill or injured animals through quality education and communication programs. Over 3,500 members strong, VeCCs has spawned three distinct national organizations ACVeCC (for veterinarians), AVeCCt (for veterinary technicians), and sveccs (for veterinary students) whose focus is on training and core knowledge in veterinary emergency and critical care medicine. For more information, visit veccs.org. Key to COsts $ indicates relative costs of any diagnostic and treatment regimens listed. $ costs less than $250 $$ costs between $250 and $500 $$$ costs between $500 and $1,000 $$$$ costs more than $1,000 APRIL 2009 VOL 11.3 standards of CARe EMERGENCY AND CRITICAL CARE MEDICINE Editorial Mission: To provide busy practitioners with concise, peer-reviewed recommendations on current treatment standards drawn from published veterinary medical literature. This publication acknowledges that standards may vary according to individual experience and practices or regional differences. The publisher is not responsible for author errors. Standards of Care: Emergency and Critical Care Medicine is published 11 times yearly (January/February is a combined issue) by Veterinary Learning Systems, 780 Township Line Road, Yardley, PA The annual subscription rate is $90. For subscription information, call , fax , info@socnewsletter.com, or visit Copyright 2009, Veterinary Learning Systems. Editor in Chief douglass K. Macintire, dvm, Ms, dacvim, dacvecc Executive Director, VECCS Gary L. stamp, dvm, Ms, dacvecc Veterinary Advisor dorothy normile, VMd, Chief Medical Officer Editorial tracey L. Giannouris, MA, Executive Editor , ext tgiannouris@vetlearn.com Kirk McKay, Managing Editor Robin A. Henry, Senior Editor Chris Reilly, Associate Editor Benjamin Hollis, Assistant Editor Design and Production Michelle taylor, Senior Art Director Bethany L. Wakeley, Studio Manager stephaney Weber, Production Artist Client Services dawn Unterreiner, Associate Production Manager Standards of Care is a refereed publication. Articles published herein have been reviewed and approved by at least two diplomates of the American College of Veterinary emergency and Critical Care. 2 A P R I L V O L U M e

3 Aggressive perianal tumors. Histopathology should be performed on all mass lesions and suspicious ulcerated lesions to rule out anal squamous cell carcinoma, perianal adenocarcinoma, and anal sac adenocarcinoma. Other injuries (e.g., bite wounds, trauma) can be ruled out by the clinical history. Most immune-mediated skin diseases affecting the mucocutaneous junctions (e.g., pemphigus vulgaris, systemic lupus erythematosus, metabolic epidermal necrosis) can be distinguished by physical examination and histopathology. Infectious agents (e.g., Pythium spp) can be ruled out by physical examination, cytology, or histopathology and culture. severe tail fold pyoderma with fistulas can be differentiated by physical examination and response to appropriate therapy. TREATMENT RECOMMENDATIONS Initial Treatment Medical management is the recommended initial treatment. Various protocols have been reported (listed below) with partial or complete remission rates of 33% 100%. Unfortunately, disease relapse is common and direct comparisons between studies cannot usually be made because drug doses and duration of follow-up vary. All therapies should be continued until complete resolution is achieved (and ideally for 4 weeks beyond complete resolution) or until there is a plateau in improvement (usually after 8+ weeks of therapy). At this point, the drug dosages may be tapered to the lowest effective dose and eventually discontinued. some dogs require chronic therapy. Prednisone at 1 2 mg/kg PO q12h followed by a gradual tapering schedule. $ Prednisone at 1 2 mg/kg PO q12h with azathioprine at 2 mg/kg PO q24h (reported duration of up to 4 weeks). Once resolution of fistulous tracts is achieved, decrease the azathioprine to 1 mg/kg q48h with a gradual tapering schedule of prednisone. $$ Azathioprine at 2 mg/kg PO q24h with metronidazole at 15 mg/kg PO q24h has been used for 7+ weeks to reduce the extent of lesions before surgical intervention. Cyclosporine (microemulsion products) alone at approximately 3 5 mg/kg PO q12h or 7.5 mg/kg PO q24h until complete resolution. $$$ Combination therapy with cyclosporine microemulsion products and ketoconazole. dosages can be adjusted every 2 to 4 weeks based on clinical signs and blood cyclosporine concentrations. Many dogs require cyclosporine dose reductions over time with more aggressive initial protocols. Initial dosage regimens include: Cyclosporine at mg/kg PO q12h and ketoconazole at 7.5 mg/kg PO q12h or 10 mg/kg PO q24h. $$ Cyclosporine at mg/kg PO q12h or 4 mg/kg q24h and ketoconazole at 8 mg/kg PO q24h. $$ some clinicians at our institution prefer to start with lower doses of ketoconazole (5 mg/kg PO q24h) combined with cyclosporine microemulsion products at 3 4 mg/kg PO q24h because the above doses of ketoconazole are relatively high for chronic therapy. tacrolimus ointment (0.1%) applied topically q12 24h. $$ Alternative/Optional Treatments/Therapy surgical intervention has been considered an initial and alternative option for the management of perianal fistulas. Most authorities consider surgery to be an option for dogs that have fistulous tracts that are resistant to medical therapy and for dogs that have anal sac involvement. numerous surgical procedures have been described, including: superficial or radical excision (anoplasty). debridement followed by fulguration or chemical cauterization. Complete tail amputation. Low tail carriage and wide tail breadth may facilitate the maintenance of a moist environment, encouraging bacterial growth and tissue damage. Supportive Treatment Antimicrobial management of secondary bacterial infections. Cephalexin, amoxicillin trihydrate/ clavulanate potassium, and metronidazole therapies have all been described. Pain management based on individual patient needs. nsaids may help alleviate pain and inflammation but must be avoided in dogs receiving glucocorticoids. Opioids (e.g., fentanyl, tramadol) may be used alone or in combination with nsaids. Gabapentin or amantadine may be used alone or in combination with nsaids or opioids. stool softeners or osmotic laxatives to facilitate passage of feces. STANDARDS of CARE: e M e R G e n C y A n d C R I t I C A L C A R e M e d I C I n e 3

4 4 An elimination diet (novel or hydrolyzed protein diet) should be considered, especially for dogs with concurrent colitis. Patient Monitoring dogs receiving cyclosporine or azathioprine as a part of their medical management should be closely monitored for adverse effects. dogs receiving cyclosporine should have blood concentrations determined if they receive moderate to high doses (i.e., > 5 mg/kg PO q24h) or appear refractory to therapy or if drug interactions are expected (e.g., when cyclosporine is administered concurrently with ketoconazole and safe dosing is difficult to predict). Cyclosporine trough (12 24 hours post pill) or peak (2 hours post pill) concentrations can be monitored within the first 2 5 days of therapy, at 2 to 4 weeks, then as needed based on clinical signs and dosage adjustments. Blood concentrations often take 2 4 weeks to stabilize following a change of dose. target trough concentrations usually vary from ng/ml, although many clinicians aim for ng/ml for dogs with perianal fistulas. Consult with the individual laboratory to verify testing methods and reference ranges as some methods overestimate the concentration of cyclosporine. several authors have reported successful therapy even with subtherapeutic dosing. trough concentrations of >600 ng/ml may increase the risk of toxicity. Intermittent biochemistry profiles (e.g., monthly for the first 2 3 months) should be considered initially, as cyclosporine may be renotoxic or hepatotoxic at high doses. the most common adverse effects of cyclosporine are GI problems (vomiting, diarrhea, anorexia) and gingival hyperplasia and papillomas with chronic use. diabetes mellitus is possible but uncommon. Azathioprine Azathioprine s primary toxic effect is on the bone marrow and the liver, with secondary effects on the GI system (vomiting, diarrhea, and pancreatitis). Complete blood counts should be monitored every 2 4 weeks for the first 3 months, then every 2 3 months. Biochemistry profiles should be performed monthly for the first 2 3 months. Ketoconazole GI problems (vomiting, diarrhea, anorexia) and hepatic injury are the most common and dosedependent adverse reactions. A P R I L V O L U M e Home Management some dogs need elizabethan collars to prevent selfmutilation during therapy. Milestones/Recovery Time Frames Partial to complete resolution varies from 33% 100%, with most protocols achieving a complete remission rate of 50%. In general, therapy with cyclosporine or tacrolimus appears to give the best overall improvement rates. early clinical improvement can be seen within 1 2 weeks. Resolution or a plateau of clinical signs may be seen around 8 16 weeks of therapy. Treatment Contraindications Cyclosporine should be used with caution in dogs with preexisting hepatic or renal disease. Care must be taken in dogs receiving other medications that are primarily metabolized by the cytochrome P450 system (e.g., ketoconazole, cimetidine, diltiazem, phenobarbital, erythromycin). Azathioprine should be used with caution in dogs with preexisting hepatic disease. Ketoconazole should be used cautiously in animals with hepatic disease and in pregnant and nursing animals. As with cyclosprine, numerous drug interactions are possible. therefore, consult a reference source before using with other drugs. PROGNOSIS Favorable Criteria early response and complete resolution of lesions. However, approximately 30% of these dogs will likely relapse. Unfavorable Criteria Lack of or poor response to medical therapy. Chronic, recurrent fistulous tracts. RECOMMENDED READING Clinical practice committee: American Gastroenterological Association medical position statement: perianal Crohn s disease. Gastroenterology 2003;125(5): doust R, Griffiths LG, sullivan M. evaluation of once daily treatment with cyclosporine for anal furunculosis in dogs. Vet Rec 2003;152(8): Hardie RJ, Gregory sp, tomlin J, et al. Cyclosporine treatment of anal furunculosis in 26 dogs. J Small Anim Pract 2005;46(6):3-9. Hedlund Cs, Fossum tw. surgery of the digestive system. In: Fossum tw, Hedlund Cs, Johnson AL, et al, eds. Small Animal Surgery. 3rd ed. st. Louis: Mosby elsevier; 2007: House AK, Guitian J, Gregory sp, Hardie RJ. evaluation of the effect of two dose rates of cyclosporine on the severity of perianal fistulae lesions and associated clinical signs in dogs. Vet Surg 2006;35(6): (continues on page 11)

5 d. fractured ribs and pulmonary contusions. e. an alveolar pattern in the right middle lung lobe. 4. Which statement is false regarding stabilization and treatment of dogs with spontaneous pneumothorax? a. If pneumothorax is suspected based on the physical examination and the patient is stable, chest radiography should be performed to confirm the diagnosis before instituting treatment. b. Propofol, acepromazine, and medetomidine should be avoided as sedative choices. c. Intermittent thoracocentesis is superior to surgical management. d. Postoperative thoracostomy tubes may be removed once negative pressure has been achieved consistently for hrs. e. Owners should be instructed to monitor their pet s respiratory rate and effort at home. 5. Which statement is true regarding heliox therapy? a. Heliox is a mixture of 80% oxygen and 20% helium gas. b. This therapy has been shown to be superior to treatment with 100% oxygen. c. The high viscosity of heliox increases laminar airflow, thereby decreasing work of breathing. d. The low density of heliox reduces turbulent airflow, thereby decreasing work of breathing. e. Heliox has a noxious odor, allowing easy detection of leaks. PERIANAL FISTULA (continued from page 4) Mathews KA, Sukhiani HRS. Randomized controlled trial of cyclosporine for treatment of perianal fistulas in dogs. JAVMA 1997;211(10): Milner HR. The role of surgery in the management of canine anal furunculosis. A review of the literature and a retrospective evaluation of treatment by surgical resection in 51 dogs. N Z Vet J 2006;54(1):1-9. Misseghers BS, Binnington AG, Mathews KA. Clinical observations of the treatment of canine perianal fistulas with topical tacrolimus in 10 dogs. Can Vet J 2000;41(8): O Neill T, Edwards GA, Holloway S. Efficacy of combined cyclosporine A and ketoconazole treatment of anal furunculosis. J Small Anim Pract 2004;45(5): Patricelli AJ, Hardie RJ, McAnulty JF. Cyclosporine and ketoconazole for the treatment of perianal fistulas in dogs. JAVMA 2002;220(7): Robson D. Review of the pharmacokinetics, interactions and adverse reactions of cyclosporine in people, dogs and cats. Vet Rec 2003;152(24): Tisdall PLC, Hunt GB, Beck JA, Malik R. Management of perianal fistulae in five dogs using azathioprine and metronidazole prior to surgery. Aust Vet J 1999;77(6): Zoran DL. Rectoanal disease. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 6th ed. St Louis: Elsevier Saunders; 2005: ARTICLE #1 CE TEST CE See box below for instructions. 1. German shepherds may be more predisposed to perianal fistulas because their perianal tissue has a. a decreased density of hair follicles. b. an increased density of apocrine glands. c. an increased density of sebaceous glands. d. decreased subcutaneous vascular beds. 2. Approximately of dogs with perianal fistulas have histopathologic evidence of colitis. a. 10% b. 50% c. 75% d. 90% 3. Diagnostic differentials for perianal fistula include a. Pythium spp infection. c. perianal tumors. b. anal sac abscesses. d. all of the above 4. Which surgical procedure has not been used to treat or manage perianal fistulas with some success? a. subtotal colectomy b. complete tail amputation c. radical excision d. debridement with fulguration 5. Which drug can be used to decrease the dosage of cyclosporine? a. itraconazole c. griseofulvin b. fluconazole d. ketoconazole The Auburn University College of Veterinary Medicine approves these articles for 1 contact hour each of continuing education credit. Those who wish to apply this credit to fulfill state relicensure requirements should consult their respective state authorities regarding applicability. Subscribers may take individual CE tests online and get real-time scores free of charge at SOCNewsletter.com. STANDARDS of CARE: E M E R G E N C Y A N D C R I T I C A L C A R E M E D I C I N E 11